The film begins with reporter Angela Vidal (Jennifer Carpenter) standing outside a fire station, introducing her special segment on firemen for the news. She keeps on messing up the introduction, and her cameraman Scott Percival (Steve Harris) walks into frame to fix her hair. As she does the introduction, she wishes they arrived earlier, since they see firefighters already leaving the station. Angela and Scott go inside the station and interview the fire chief, who tells them that 5% of the calls they receive are for medical emergencies, and they answer them because most firemen now are trained paramedics. He then lets Angela slide down the fire pole, which makes her giddy. The chief takes them to the cafeteria, where all the firemen are eating. They get all riled up when they see the news crew. The chief introduces Angela to Fletcher (Jonathan Schaech) and Jake (Jay Hernandez), who are the two firemen they will be following for the night. After dinner, Angela and Scott hook microphones to Jake and Fletcher. Angela tells them to keep their profanity to a minimum, since it will be easier to edit. Fletcher and Jake show them an old hook ladder used in the past by the fire department (basically a large hook attached to a pole, which the firefighters would use to climb into buildings). The firemen also show Angela their dog and explain that it’s more of a mascot now, since Dalmatians used to go with the firefighters back in the day when they would ride horses. Fletcher has the Dalmatian demonstrate stop, drop, and roll in case of a fire. Jake shows Angela around the station and explains how the firefighters have everything they need at the station (beds, showers, a racquet ball court, e.t.c…).
Eventually, Angela grows bored since nothing’s happening. She sees Fletcher and Jake talking in the distance while washing their fire truck. Angela listens to Scott’s earpiece and hears Fletcher betting that he can have sex with her by the time the night’s over. Angela busts him, but Fletcher keeps on hitting her. While at the station, Fletcher and Angela have a race to see who can get into a fire suit the fastest. Angela wins, so Fletcher pays her ten bucks. Fletcher and Jake show her the bathroom, where various firemen are just finishing showering. One fireman repeatedly flashes himself to the crew. Time passes, and Angela gets bored again. She sees a fireman stepping out of his room to use the bathroom. She peeks inside the room with Scott and sees that it’s smaller than what her dorm room was. Suddenly, the alarm goes off at the station. Fletcher, Jake, and two more firefighters get a call. Angela and Scott rush downstairs to get in the back of the fire truck. While driving, Fletcher says that the call is for a medical emergency at an apartment building. He then says that the firemen have a chick-o-meter, so they rate all the women they drive by. The firefighters and the crew arrive at the apartment building, where Yuri (Rade Serbedzija) is waiting outside. He was the one who called in the emergency, since there was a woman screaming horrifically upstairs. Fletcher, Jake, Angela, Scott, and Yuri enter the building while the other two firefighters wait outside. In the lobby of the building are a group of concerned tenants. There are already two police officers on the scene James (Andrew Fiscella) and Danny (Columbus Short). James tells Jake that the reporters are his problem, and if he tells them not to film something, they have to obey. The firefighters, the reporters, James, and Yuri all go upstairs to where the screaming was. Danny has been waiting outside the apartment for the others to show up. They try to get Ms. Espinoza to open the door, but they don’t hear any movement. Yuri tries to open the door with a master key, but it doesn’t work. As Angela rushes to get coverage and introduce the situation to the camera, she is startled when Jake breaks through the door with a sledgehammer.
They all enter the apartment and then get startled by a dog running out the door. They find Ms. Espinoza (Jeannie Epper) in the living room, and hear her struggling to breathe. They can’t quite see her face due to the dim lights, and so Scott turns on the light for his camera. Once the light is flashed in Espinoza’s face, she freaks out and growls. James has Scott turn the light off, and then he tries to approach her. Espinoza is foaming at the mouth, crying, and has blood on her shirt. She suddenly lunges at James and bites a chunk of his neck out. The others fight her off of him and thrown her on the floor. Jake and Danny carry James downstairs while the crew follows. Fletcher remains alone in the apartment with Espinoza. On the way down, Angela urges Scott to film everything. They get to the lobby of the building and try to go out the front door, but find that the authorities have arrived and have locked them in. A voice tells them not to try to leave the building, and everything will be alright. Danny tries to tell them that there’s an injured police officer that needs medical attention, but they won’t respond to him. The tenants are freaking out and don’t understand why they are being kept in the building. Lawrence (Greg Germann), a vet, does his best to tend to James’ wound. Fletcher’s body suddenly falls down the staircase and splatters on the ground. Jake rushes over to him and finds that his face has been bitten. A pool of blood emerges from Fletcher’s head, and he has Lawrence tend to him. Danny and Jake decide to go upstairs to subdue Espinoza, and they order the reporters to stay with everyone else downstairs.
After a little while, Angela and Scott sneak upstairs back to Espinoza’s apartment. They hear things being broken inside, and they slowly enter. The cleaning lady suddenly runs in front of them and falls to the floor dead. Danny and Jake show up and get after the reporters for not listening to them. Then they see Espinoza in the apartment, blood covering her mouth and throat. Danny draws his pistol and orders her to calm down. Espinoza charges at them, and so Danny shoots her three times in the chest, killing her. He’s in shock over what happened, and then he attacks Scott for having the camera in his face. Jake gets him to calm down and go downstairs, leaving Angela frozen in the apartment. A rat scrambles towards Scott, but he kills it by stomping on it. Scott tells her that they need to go, but Angela wants to see the footage of the shooting. On their way downstairs, Angela runs into Sadie (Dania Ramirez) and tells her to come to the lobby with them. Everyone winds up back downstairs, and they all grow desperate to find out what’s going on. Fletcher and James are still alive, but they’ve lost a lot of blood. All the windows and doors are being sealed by the authorities outside, and whenever someone gets too close to the windows they are forced back at gunpoint. All their cell phones are jammed. Jake realizes that they’re being quarantined because the authorities think there’s a biological or chemical emergency inside. Jake goes door to door for all the apartments and tells those who are still there to come downstairs with everyone else. The tenants are Yuri, Lawrence, Wanda (Elaine Kagan), drunk lawyer Randy (Denis O’Hare), little girl Briana (Joey King), her mother Kathy (Marin Hinkle), Bernard (Bernard White), Sadie, and African couple Nadif (Jermaine Jackson) and Jwahir (Sharon Ferguson) neither of whom speak English. Jake, Angela, and Scott go to another apartment to get Elise (Stacy Chbosky) to come downstairs as well, but she remains unresponsive. They find Elise sitting on her couch, watching the static on her TV, and foaming at the mouth. Jake and Angela wind up carrying her downstairs.
On the first floor is a textile shop in the back, which Yuri opens up. They put Fletcher, James, and Elise in the shop. Lawrence does his best to clean up their wounds, but since he’s a veterinarian that’s all he can do until they get real medical attention. Yuri tells Jake that there might be a way out, and leads them upstairs to an apartment. If they go out the window, they can jump down to the patio outside. Yuri, Jake, Angela, and Scott sneak around and make sure not to make themselves noticed by the authorities. However, a helicopter suddenly shines a light on them and men with machine guns order the group back. Angela tries to ask them what’s going on, but they won’t tell her. She says that they’re filming everything and people will see what they’re doing to them. The authorities seal up the windows, and Danny finds them. He orders the group to go back downstairs, but they want him to tell them what’s happening. He doesn’t know, and everyone starts to get hostile. Danny pulls out his gun and orders them back. Jake calms him down, and Danny apologizes. They go downstairs, and Angela starts to interview the tenants. Briana is sick with a fever, and has a dog named Max. Her dog is sick, and so her father took him to an animal hospital. Kathy accidentally interrupts the interview by talking off-camera. Bernard is an opera teacher, and he’s sleeping with Sadie, who’s his best student. Lawrence says that he thinks he knows what’s going on. He goes over the symptoms for the sick/injured, and says that they’re characteristics of rabies. However, rabies takes a while to act, not in minutes like with what’s happening to them.
Randy keeps on getting in Danny’s face and demands to be let back into his apartment. Danny says that it’s safer for everyone to stick together. While Scott films this, he and Angela see Bernard and Sadie sneaking away through the textile shop. They follow them, and Sadie says that they have an antenna TV, so they can try to see what’s going on outside. While walking to their apartment, they come across Espinoza’s rabid dog. It growls at them, and then Randy show up on their floor in the elevator. They try to warn him away, but it’s too late. The dog attacks Randy and the elevator doors close. They hear Randy scream as he is mauled to death. They make their way into Bernard’s apartment, and they come across Elise. She tries to attack Angela, but she throws her off. Scott then bashes Elise’s face in with the camera, killing her. He wipes the blood off the camera lens and Angela takes off her shirt since it has blood on it. They briefly see a news report on the building on Bernard’s TV. The chief of police tells the reporters that everyone has been evacuated from the building. Angela wonders why he would lie about it. The power is shut off. They go back downstairs, and Fletcher suddenly is on his feet again. His leg is broken and the bone is sticking out of his body. His foot looks close to snapping off, but he’s foaming at the mouth and tries to grab anyone. Jake holds him down and Lawrence injects a sedative into his neck, causing him to fall asleep. Everyone is rounded up in the textile shop, and Danny tells them that he has some good news. The authorities have said that they will be sending in some CDC (Center for Disease Control) agents to conduct some blood tests. If they see that they are not infected, they will probably be let go. Lawrence says that the blood tests wouldn’t work for rabies. The only way to test for that is to get a brain sample. Danny tells him to be quiet, since they still don’t really know what they’re dealing with. Danny and Jake have a roll call to see if everyone is still there. The African couple still has their elderly/sick father in their apartment. Danny asks Yuri who owns the penthouse upstairs. He says that a man from Boston lives there, but he hasn’t seen him around in a while.
The front door to the building is opened, and everyone is held back at gunpoint. Two CDC agents enter the building wearing gas masks and completely covered head-to-toe in suits. The door is sealed again behind them. Danny and Jake lead them to the textile shop and shut the door. Angela cracks open the door so that they can document what’s going on, but Danny shuts it again. Angela and Scott go to the room next door. Scott climbs on top of a table and films what’s going on through an opened window. They see the CDC agents handcuffing James and Fletcher to railings. An agent injects Fletcher with a sedative, and then drills into his head. He collects some brain matter and removes the drill. Fletcher suddenly attacks an agent and bites his neck. Danny, Jake, and the other CDC agent run out of the room. The agent locks Lawrence inside, even though he wasn’t bitten. He tells him to just keep away from the infected, but then he’s attacked by someone. James spits blood on the door and breaks through it. Everyone closes the shutters for the textile shop and then they demand the agent to explain what’s going on. He says that a sick dog was brought to a vet, and it was unlike anything they’ve seen before. The dog attacked all the other animals, and then they became increasingly aggressive. They traced the dog’s collar back to the building, and so they quarantined it. He says that the dog’s name was Max.
Everyone looks at Kathy, who’s holding Briana. Kathy remains adamant that Briana just has a fever and is not sick like the others. Suddenly, Briana bites Kathy’s face and runs upstairs. The agent gives Danny a needle and tells him to stick Briana with it. Danny also handcuffs Kathy to the railing of the stairs while she pleads for them not to hurt her little girl. Danny, Jake, Angela, and Scott go upstairs and wind up back in Espinoza’s apartment again. However, they see that Espinoza’s body is gone. They search around for Briana and then find her standing silently. She’s foaming at the mouth, and Danny approaches her. She bites Danny’s neck, and he urges everyone to leave while he fights Briana. Espinoza appears at the door, and Jake smashes her face in with the sledgehammer. They run down the stairs, but the tenants are all running up the stairs, screaming for them to go back. Jake, Angela, and Scott make it downstairs and see that the infected are breaking their way through the shutter. Jake kicks infected Lawrence’s face a couple of times, but it’s no use. Nadif is bitten while trying to keep them at bay. Jake, Angela, and Scott decide to run upstairs. However, Kathy is still handcuffed to the railing. Danny still has the key, so she’s helpless. They run away just as the infected break through the shutter and eat Kathy. Angela, Jake, Scott, Yuri, Wanda, Bernard, Sadie, and the agent wind up locking themselves in a room. It turns out that the agent was bitten, and so they lock him in an adjacent room. Jake asks if anyone else was bit, but everyone says no.
It turns out that Sadie was bitten, and her hand was mangled by one of the infected. Yuri tells Jake to kill her, but Bernard pleads with him not to. Out of desperation, he opens the window and cuts through the seal, yelling out for help. A sniper on the rooftop across the street shoots Bernard through the forehead, killing him. He then fires at the others, but misses. Angela realizes that they’re not going to get out of there alive. Yuri says that he’s thought of another way to escape. There’s a place in the basement that leads to the sewers. They can get the key to the basement from his apartment. The infected agent suddenly bursts through the glass door between them and bites Yuri. Sadie also fully turns and attacks Wanda. Jake, Angela, and Scott run downstairs past Kathy’s body. Jake beats Nadif with the sledgehammer and they try to figure out which apartment Yuri lived in by looking at the mail boxes. They finally figure it out and go to the stairs, but infected Kathy suddenly stands up and tries to attack them (but is held back due to the handcuffs). They make their way to the elevator, and Jake kills the rabid dog with the sledgehammer. The doors won’t close right away, and so he bashes the infected that run up to them. They go upstairs and are attacked by Sadie. Jake repeatedly punches her in the face and throws her in the elevator while they get out. However, Sadie still comes back for more, and so Jake winds up strangling her and breaking her neck. Angela is scared that she was bitten, but Scott reassures her that she wasn’t. They make it to Yuri’s apartment, and infected Jwahir attacks them. Scott knocks her over the railing and she falls to the lower level. As Jake fights off another infected person, Angela and Scott search for the keys to the basement. They find a ring full of keys and decide to take the whole thing.
Jake is surprised by infected Yuri, who bites his neck. Angela and Scott see that all the infected are on the stairway and are running up to them. With no choice, they retreat to the penthouse apartment and get inside before infected Danny can reach them. Scott says that since the apartment is empty, they’re no longer in danger and can wait it out. In the penthouse, they find various cages with animals. They also find some newspaper clippings, which state that a doomsday cult broke into a research facility and stole something. Another clipping says that the cult is working on an Armageddon virus. Deeper into the penthouse are various tools and tables, which makes it apparent that the owner is part of the cult and was working on the virus. Suddenly, the attic door swings open. Angela doesn’t want to be left in the dark, since the only light is from Scott’s camera. He tells her that he’s going to look inside the attic to see if maybe they can hide there. Scott slowly moves the camera around the attic. An infected boy screeches at him and claws at the camera, destroying the light. Angela freaks out, and Scott turns on the night vision. He tells her to be quiet, since he hears something coming from another room. An extremely thin infected man (Doug Jones) enters their room, knocking things over and making loud noises. It looks like he was the first to be infected with the virus. He walks by Angela and Scott, but since they are quiet he can’t find them. Scott tries to guide them past the man, but Angela accidentally makes a noise. The infected man suddenly attacks Scott and then throws him away, causing the camera to fall to the floor. Angela grabs the camera and uses the night vision to see. She sees the infected man eating Scott and grows terrified. He then viciously attacks Angela, causing her to drop the camera. Angela winds up on the floor and slowly crawls towards the camera. The film ends with Angela suddenly being dragged away and presumably killed.
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