In The Silence of the Lambs, Clarice Starling tells Dr. Hannibal Lecter that she was raised in a small town in West Virginia with her father, a police officer. When she was about 10 years old, her father was shot during to a robbery. He died a month after the incident. Starling was sent to live with her uncle on a Montana sheep and horse farm. She briefly ran away in horror when she witnessed the lambs being slaughtered (the title of the book and movie refer to her being haunted by the screaming she heard from the lambs).

Also in the movie, Starling is a student at the FBI Academy. She hopes to work at the Behavioral Science Unit, tracking down serial killers and ultimately apprehending them. Her mentor, FBI director Jack Crawford, sends her to interview Dr. Hannibal Lecter, a brilliant psychiatrist and cannibalistic serial killer. He is housed in a wing of a Baltimore mental institution.

Upon arriving at the asylum for her first interview with Lecter, the asylum manager Frederick Chilton makes a crude pass at her, which she rebuffs. This helps her bond with Lecter, who also despises Chilton. As time passes, Lecter gives Starling information about Buffalo Bill, a currently active serial killer being hunted by the FBI. He does this only in exchange for personal information, which Jack Crawford has specifically warned Clarice to keep secret from Lecter.

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