Meanwhile, five college students — Dana (Kristen Connolly), Curt (Chris Hemsworth), Jules (Anna Hutchison), Marty (Fran Kranz), and Holden (Jesse Williams) — drive out for a vacation to a remote cabin in the woods, while the technicians keep an eye on the students with hidden cameras.
At the cabin, the friends party until they find a cellar full of creepy old artifacts. Dana reads an incantation from an old diary, which causes zombies to rise from the grave. The technicians continue to watch the proceedings while excitedly betting on the actions of the students, including which of a list of different monsters would be chosen and who would make the choice.
Curt and Jules go outside to have sex while the technicians administer drugs via a ventilation system to influence the victims’ actions. Zombies attack the lovers and Jules is killed. Meanwhile, in the cabin, the paranoid Marty begins to feel as if things are being controlled by "puppeteers" and goes outside, where he runs into the fleeing Curt and a zombie. The friends attempt to barricade the cabin against the zombies while the technicians attempt to bring about their deaths. Marty finds a surveillance camera in his room, confirming his paranoid fantasies, but he is attacked and presumably killed off-screen. Holden, Dana, and Curt flee in their RV.
They get as far as a long mountain tunnel but the technicians blow up the tunnel and the escape route is blocked. Curt uses his motorbike to jump the gap in the exit road but as he jumps, he runs into an enormous force field that kills him, and Holden and Dana realize something much greater is happening than they had believed. Dana now believes Marty's talk of "puppeteers." A zombie kills Holden and the RV crashes into the lake. The technicians drink in celebration that they have completed the "ritual," while the screens in the background show Dana fighting for her life with the zombie. The party soon stops when a phone call from "upstairs" informs them that Marty is still alive, and he rescues Dana.
It turns out that Marty came across a hidden control box near the cabin from which he was able to access an elevator with glass walls. He and Dana take it down to the facility where the technicians are, and as they do so, they pass by a number of monsters, each of which corresponds to an artifact from the cellar. Their glass elevator is but one of many pods, each containing a monster. Dana and Marty escape the elevator but are cornered by a SWAT team. To escape, they release the monsters in all the pods, who start killing everyone in the facility.
Dana and Marty find a large crypt with strange tablets and meet the "Director" (Sigourney Weaver). She tells them the reason for the ritual is to appease gods called "The Ancient Ones" who live beneath the facility and want the annual sacrifice of five young people who comprise certain archetypes: The Athlete, The Whore, The Scholar, The Fool, and The Virgin. The Ancient Ones will rise and destroy the world unless the ritual is completed, meaning that Marty must die before sunrise. The Director urges Dana to kill Marty in order to save all of humanity.
Dana aims her gun at Marty but hesitates. The Director tries to kill Marty while Dana is attacked by a werewolf. Marty saves her and the Director is attacked by a zombie and Marty knocks both zombie and Director off the platform and into the abode of the Ancient Ones.
Marty sits and comforts Dana while also lighting a joint. He then remarks that this course of action might be for the best, that it might be better for someone else to get a chance at life. Morning comes and Marty and Dana hold each other as a gigantic hand from one of the Ancient Ones rises up and destroys the facility and cabin.
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