Newlyweds Leo and Teresa are touring the most haunted spots in America and visit Briarcliff Manor on the East Coast. The building was constructed in 1908 as a tuberculosis ward and was then purchased by the Catholic Church and used as a sanitarium. Leo remembers that the most famous resident was Bloody Face, a serial killer.
The couple finds the shock theater and Leo playfully straps Teresa in. They begin to have sex but Teresa hears something. They go to investigate and hear noises coming from behind a closed cell door. Leo opens the cell window and extends Teresa's cell phone through to provide a light, and he sees something move on the screen. Before he can withdraw his arm, the thing inside grabs it and pulls it off.
Kit Walker is closing up the gas station where he works for the night. A gang of local thugs, led by Bill, sneak in, startling Kit. He threatens to shoot them with his gun and Billy tells him that they're going after a black man who messed with a friend's sister. Kit refuses to go with them or loan them his gun. As he goes, Billy takes a chocolate bar and comments that Kit has a new maid, and then leaves with his friends.
Kit goes home to where his new black wife, Alma, is cooking supper. He wants to tell everyone that they're married but she warns him that the world isn't ready to hear about interracial marriages. They go to the bedroom to make love. Afterward, Alma goes back to the kitchen and Kit hears something moving outside. The radio bursts into static and Kit grabs a shotgun and goes to investigate, figuring that it's Billy and the others. When he gets outside, a bright light shines down from the sky. Alma screams for help and Kit runs inside, and a vast noise slams down on him, deafening him and knocking him to the floor. It stops and Kit starts to get up, but some force picks him, slams him into the ceiling, and then drops him.
Sometime later, reporter Lana Winters visits Briarcliff to do a story about the bakery run by Sister Jude. As Lana goes inside, a young patient, Pepper, tries to play with her. Sister Mary Eunice comes out and tells Pepper to leave Lana alone. She warns the reporter that Pepper sliced her baby sister's ears off and tried to drown her, and then leads Lana up to Sister Jude's office. Jude is busy shaving the hair off of a girl, Shelley. The nun stops when they enter and tells Mary Eunice to knock the next time. She lets Shelley go with only some of her hair shaved off, but Shelley says that Jude can't make her ashamed of what she's done.
As Mary Eunice takes Shelley to the common room, Jude tells Lana that Shelley has been diagnoses as a nymphomaniac but she believes that the girl simply suffers from the sin of lust. Lana discusses the bakery and Jude explains that Monsignor Timothy Howard was the one who created the bakery and has even more plans for Briarcliff. Mary Eunice bursts back in and tells Jude that the bad person will be arriving in a few minutes.
Lana realizes that the person she really came to see, Bloody Face, is being brought there. She reminds Jude that the killer decapitated three women and that the community wants to know about him. Jude realizes that Lana isn't there to talk about the bakery and orders her out. Lana begs for a few minutes with the killer and Jude tells her that the authorities have sentenced Bloody Face to Briarcliff for observation until he's fit to stand trial. Everyone goes outside and watches as the prison guards bring in the killer: Kit. He's taken inside, showered, deloused, and drugged unconscious. Later, Jude comes to see him. He insists that he didn't kill anyone but the nun tells him that he will repent before God. Kit claims that little green men abducted him but Jude says that he's the only monster and asks if Alma died as easily as the white girls. When he spits on her and she takes out a crop and beats him.
The orderlies take Kit to the common room and Shelley approaches him, offering sex. He tells her to get away and starts to smash the record player, which is endlessly playing a French tune. One patient, Grace, comes over and warns him not to do it or he'll get more lashes. As she assures Kit that she's not crazy, another patient, Spivey, comes over and taunts Kit about Alma's death. Kit attacks him and the two men fight until Jude and the orderlies arrive to break it up. Kit insists that he didn't start the fight but Jude has the orderlies beat him and haul him away.
Kit wakes up later in solitary, in a straitjacket. Grace arrives and slips some food to him through the slot, and explains that she got to him by volunteering for kitchen detail. She offers Kit a cigarette and says that she's being nice to him because she hopes it will come back to him. Kit wonders what she did to get sent to Briarcliff and Grace tells him that they claimed she chopped up her family. She says that she didn't do it and asks if he killed Alma, and Kit says he didn't do it. When he says that he's sane, Grace warns him that's the worst thing to be because they'll treat him far worse. She leaves but promises to come back if she can.
Jude finds Mary Eunice in tears and the young nurse explains that Willie has disappeared since Dr. Arthur Arden has taken the patient to the medical wing. The older nun goes to see Arden in his combination lab and conservatory and demands to see Willie. Arden refuses, saying that Howard gave him a free hand with his medical experiments. He shows Jude his plant, which he has created by bombarding with gamma rays. Jude insists that she needs to know what is happening to the patients so that she can manage Briarcliff, and Arden tells her that Willie and three other patients in his care died. He then had the bodies cremated, but Jude finds it convenient that none of them had any families to miss them. She promises to find out what he's doing and bring him up on charges.
Lana goes to the apartment that she shares with her lover, local teacher Wendy Paisa. The reporter discusses the story she thinks she can write about Briarcliff but both women agree that her editor will never publish it. Lana plans to pursue it and Wendy assures her that she'll give her the time to pursue it. As they start to kiss, Wendy reminds Lana to close the blinds for fear that someone might see them. Once they do so, Lana tells Wendy that everything she does is because Wendy loves her.
Jude is in the kitchen making a special meal and praying. She then applies perfume to herself and serves supper to Monsignor Howard. They discuss Arden and Howard says that it's a new era of science, which comes from God, and that their superiors have vouched for Arden. Howard compliments Jude on the food and then tells her that he wants Briarcliff to become so renowned that he can parley it into a promotion to Cardinal of New York so that he can ultimately become Pope. He promises Jude that she will be with him all the way, and Jude imagines making love to the monsignor.
Arden summons Mary Eunice to his chambers and they listen to growling noises outside. He tells her that they need some meat and the weather is changing, and sends Mary Eunice out with buckets of meat. She sets them down and something emerges from the bushes, and the nun runs back to Briarcliff. Lana is waiting for her and asks what is in the woods, but Mary Eunice says that they have to go immediately and leads her into the house.
Kit tries to eat what food he can but is interrupted when Arden comes in. The doctor injects Kit with a sedative and tells him that he shouldn't be in a cell when there is so much to learn.
Teresa stops the bleeding as best she can and realizes that Leo's phone is missing and hers is in the cell. She runs to the outside doors only to discover that someone has chained them shut. Desperate, Teresa finally locates a door but it leads her into the tunnels beneath the manor.
Mary Eunice leads Lana into the tunnels beneath the manor and ignores the reporter's questions. The reporter blackmails her into giving her time to look around in return for her silence to Jude about what Mary Eunice has been up to, and the nun agrees to help.
Arden takes Kit to his operating theater and explains that he runs the place and Jude doesn't. He assures Kit that Jude is powerless to do anything with him because they live in a time of science, and secures Kit's head with a harness. He apologizes for what comes next because he can't use anesthetic because it interferes with his readings.
Mary Eunice leads Lana to the men's ward, sneaking by Jude on her nightly patrols. Spivey calls out to them from his cell and throws excrement on Mary Eunice. Sobbing, she runs off after telling Lana to stand still. However, the reporter ignores her and goes on into the men's ward. An orderly emerges from the empty cell where he was having sex with Shelley and asks what Lana is doing there. She blackmails him, promising not to tell Jude what he's been doing, and the orderly quickly leaves. When Shelley comes out, Lana asks her where Bloody Face is and Shelley says that Lana can find her in solitary. Jude enters the ward and Shelley runs off while Lana hides in the empty cell, avoiding detection.
Arden tells Kit that he is trying to find evil in the occipital lobes. The doctor proudly shows off the ten brains that he has in jars but admits that the evil within them pales compared to what is in Kit's mind. He activates his machinery and Kit finds himself naked in a white voice. Alma appears briefly, begging him for help, and then fades away. While Kit hallucinates, Arden examines him and finds a hard lump in his neck. He cuts open the skin and finds a small black hexagonal chip. As the doctor stares at it, it sprouts filament legs and runs away.
When Lana opens the window to Kit's cell, something grabs her.
The next morning, Jude calls Mary Eunice in and warns her that she's putting their plans at risk. The younger nun is sobbing and Jude wonders if she made a poor decision by choosing not to see Mary Eunice's stupidity. Mary Eunice takes out Jude's largest crop and offers herself for a beating, calling herself stupid. The older nun tells her to get out and warns her that if she ever hears Mary Eunice call herself stupid, she will beat her.
When Lana wakes up, she finds herself in traction in a bed. Jude is at her side and tells her that she had an attack. Lana insists that someone attacked her but the nun dismisses it as errant imagination. The reporter warns that people know where she is and demands to be released, but Jude, unconcerned, says that she will be spending her long recovery with them.
Earlier, Jude goes to Wendy's house and threatens the teacher with the exposure of her lesbian affair. After making sure that Lana is not in touch with her family, Jude tells Wendy to sign commitment papers as a respected member of the community. Wendy refuses at first but finally caves
Jude shows Lana the commitment papers and assures her that they will soon cure her of her homosexuality. As Jude leaves, smiling in satisfaction, Mary Eunice gives her a ring of keys and apologizes for stealing. Jude uses them to go into the chamber that Arden is currently using. The walls are covered in scratches and he's disinfecting everything, but denies that anything was living there. Jude warns him that she will expose him for what he is but Arden simply takes the keys and walks away.
While Leo lies on the floor in shock, Teresa runs down the tunnel only to find Bloody Face blocking her path.