REC revolves around a television reporter, Ángela Vidal, and her cameraman, Pablo, who cover the night shift in one of Barcelona's local fire stations for the fictional documentary television series 'While You Sleep'. The firehouse receives a call from an apartment building about a woman who is trapped. When they arrive, the police break down the door, with Ángela and Pablo recording their actions. The woman becomes extraordinarily aggressive and bites one of the policemen. Meanwhile, the terrified residents gather in the entrance hall, and look on as the police and military seal off the building. The firefighter who remained at the old lady's apartment is bitten and tossed down the stairs. The camera crew, the remaining cop and the second firefighter go up again and are attacked. The cop aparently kills the old lady with a shot, which is confirmed by Ángela who asks Pablo to rewind and replay that part of the tape. The camera crew remain trapped inside the building with the residents, and continue recording in spite of police pressure. Ángela interviews a little girl named Jennifer who lives with her parents and dog in the building. Jennifer is ill with what her mother claims is tonsilitis. She says her dog, Max, is at the veterinarian because he appeared to be sick as well. A health inspector wearing a hazmat suit arrives and attempts to treat the injured, who become fiercely violent despite their critical injuries. The health inspector explains that the time the disease takes to cause sickness depends on blood type. The health inspector also reveals that, sometime during the previous day, a dog with the illness was taken to the veterinarian; the dog became violent and attacked and killed other pets at the clinic. The dog was euthanized, and was traced back to the apartment building. Jennifer, the girl who owned the dog, then suddenly attacks her mother. The inspector tells the distraught residents that this unknown but virulent disease is infecting people, causing them to turn into bloodthirsty savages. More and more people in the building become infected, and Ángela and Pablo are forced to fight them off. They find out that some of the corpses have disappeared and soon discover that the people presumed dead are now infected and chasing them. Eventually they learn that there is a key to a door in the apartment building workshop, which leads to an exit via the sewer system. However, the key is located on the third floor in a resident's apartment.
After finding the key, Ángela and Pablo appear to be the only human survivors, everyone else being dead or infected. Rather than making their way to the workshop, they are forced upstairs to the penthouse by the remaining infected. They then search the penthouse, and discover that its former owner was an agent of the Vatican who was charged with researching and isolating a suspected virus believed to be the biological cause of demonic possession, which was later confirmed to exist in a young girl who was supposedly possessed. The agent kidnapped and brought the girl to the penthouse to conduct his research and to possibly cure her; unfortunately, during the work the virus managed to mutate and become contagious. A door to the attic opens, and Pablo uses his camera to look inside. Something jumps at the camera and breaks its light. Pablo turns on the night vision to see in the dark and discovers the sealed door referenced earlier by the agent on an audio tape. The agent abandoned his efforts to cure the girl after failing to engineer a vaccine and sealed her in the room before leaving the city. The girl, now a ghoulishly emaciated figure, begins searching the kitchen area, unaware of Ángela and Pablo's presence. Pablo tries to escape, but trips and is viciously attacked by the girl, making Pablo drop the camera. Ángela picks it up and runs, only to trip and drop the camera as well. She searches for it but is unable to find it. The camera continues to record as the screams of the infected girl are heard and Ángela is dragged into the darkness, screaming.
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