Clarice Starling is an agent in training at the F.B.I. Academy in Quantico. She is taken out of training by Jack Crawford who is head of the Behavioral Science Unit because he wants her to go to the Baltimore State hospital for the Criminally Insane to interview Hannibal "the Cannibal" Lecter; Dr Lecter is a serial killer who eats his victims, but he was previously a psychiatrist and is therefore an expert in playing mind games. Crawford believes Lecter can help them catch an active serial killer nicknamed Buffalo Bill who skins his victims, all of whom are women.
Starling is taken to Lecter's cell by Frederick Chilton the prison director. Lecter is nice at first but soon sees through her basic attempts to analyze him, and he becomes angry. He won't help her but as she leaves, another prisoner flicks semen in her direction, which he considers rude; he calls Clarice back to his cell and tells her to look for an old patient of his. In seeking the patient she finds a storage shed which contains the severed head of a man with a sphinx moth in its throat. When she returns to visit Lecter again he tells her that the man is connected to Buffalo Bill, and that he has decided to help her on the condition that he is transferred to another prison facility because he wants to be away from Chilton.
Catherine Martin, daughter of a senator, is abducted, and the abductor is believed to be Buffalo Bill. Crawford tells Starling to offer Lecter a fake deal; a prison transfer in exchange for information that leads to Martin's rescue. Lecter doesn't like the deal; he wants to play a game with Starling instead. For every piece of information he gives her about Buffalo Bill, she will have to give him a piece of information about herself. She agrees and tells him about her father's murder which occurred when she was only ten years old. Chilton secretly records the conversation then tells Lecter that Starling is lying to him and that the deal she has offered him is fake. He offers Lecter a deal of his own instead; Lecter agrees to the deal and is immediately flown to Memphis. He taunts Senator Martin, and gives her information about Buffalo Bill, telling her that his real name is Louis Friend.
Starling is troubled by the revelation and realizes that "Louis Friend" is an anagram of iron sulfide, another name for Fool's Gold. She visits Lecter, who is held in a cage in the center of a large room in the Tennessee Courthouse. She demands he tells her the truth but he refuses to give her any information until she resumes the information exchange they were playing before. He also tells her that Buffalo Bill's identity is in the case file. She tells him about an incident in her childhood when she was awoken by the sound of spring lambs being slaughtered on a farm in Montana. She still hears the lambs screaming sometimes in her nightmares. Lecter becomes the psychiatrist again and tells her that she is trying so hard to save Catherine because she believes that if she does then the screaming of the lambs will stop. He returns the case file to her, minus a paper clip, which he uses later to unlock his cage door; free, he kills the guards assigned to keep him prisoner. He disappears.
After reading the notes that Lecter has made in the case file, Starling realizes that Buffalo Bill knew his first victim. After visiting the victim's home town she learns that Buffalo Bill was a tailor and that he has made dress patterns, and segments of dresses, the same size and shape as the pieces of skin removed from each of his victims. He is making himself a "woman suit". She calls Crawford to tell him this but he has already made the discovery for himself, having cross-referenced Lecter's notes with hospital records and learned about a trans-sexual woman by the name of Jame Gumb, who had applied for gender reassignment surgery but had been turned down. Crawford leads an F.B.I. team to Gumb's address in Illinois whilst Starling continues to interview the first victim's friends and acquaintances. Her search leads her to the home of one Jack Gordon, but looking around his house she discovers a sphinx moth and she realizes that she is actually in the home of Buffalo Bill. She finds Catherine Martin in the basement, still alive but with a broken ankle. Gumb is in the basement too; he turns off the lights and dons night vision goggles so that he can stalk Starling in the dark. She can't see him but she hears the sound of him cocking his gun and reacts in time to shoot him dead before he is able to fire at her.
Starling goes on to graduate from the Academy but during a celebration party receives a telephone call from Lecter. He is at an airport in Bimini and is calling to tell Clarice that he has no plans to come after her. All he asks is that she agrees not to come after him. She refuses to take the deal. He abruptly ends the call telling her he is having an old friend for dinner; Chilton is also in Bimini, and Lecter begins to follow him, both men disappearing into the melee.
