In 1899, an Oxford University professor demonstrates a case of female hysteria, Lady (Eliza) Graves (Kate Beckinsale), before his class. The patient is drugged and protesting that she is sane, but the professor points out that all mental patients claim to be sane, much as all criminals claim to be innocent. He ignores her demands that he not touch her to induce a fit for the students to observe. The professor advises his students to believe nothing they hear and only half of what they see.

Later, a young man, the newly-minted Dr. Edward Newgate, (Jim Sturgess), arrives at Stonehearst Asylum on Christmas, where he desires to take up residency. A group of armed men led by Mickey Finn (David Thewlis) allow him entry. Finn escorts him to the office of the superintendent, Dr. Silas Lamb (Ben Kingsley). Although Lamb was not expecting him, despite Newgate having sent letters preceding his arrival, he welcomes the help of an Oxford-educated doctor and grants him the residency.

Newgate is surprised by Lamb's unorthodox methods and uncustomarily humane asylum. Lamb explains that he does not believe in drugging or incarcerating his patients, and he encourages their delusions when he feels it will bring them greater happiness, thus creating a kind and dignified environment at the asylum.

Lady Graves, now a resident at Stonehearst, is introduced to Newgate, who appears immediately smitten. Lamb explains that the Lady Graves has an abusive and painful past. She developed hysteria from enduring her husband's "unnatural appetites" and can no longer bear emotional or physical contact without seizing in hysterical fits. She stabbed her husband in the right eye with a comb and bit off his left ear trying to protect herself, which led to her father committing her into the asylum to escape her marriage to her "monster" of a husband. Her husband has since been trying to free her back into his care. Dr. Lamb is currently prescribing musical therapy for her and refuses to declare her sane, for her own safety.

Though she brushes aside Newgate's attempts at flirtation, she is struck by his empathy and respectful demeanor. An elaborate Christmas feast follows, during which the staff and patients mingle and a small fight between Newgate and Finn occurs, cementing their dislike for one another. After the dinner, Lady Graves delivers ominous warnings to Newgate, and quietly insists that he flee the asylum, but Newgate refuses to leave without her.

The reason for Lady Graves' warning soon reveals itself. Newgate discovers dozens of prisoners being kept in basement cells. The prisoners reveal that they are the true staff of Stonehearst, and the doctors and nurses Newgate has met upstairs are actually patients.

The real superintendent, Dr. Benjamin Salt (Michael Caine), explains that Lamb and Finn drugged their drinks and led a revolt. Dr. Salt and Mrs. Pike (Sin

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