Set in 1761 in London, the film focuses on events at St. Mary's of Bethlehem Asylum, a fictionalized version of Bethlem Royal Hospital, also known as "Bedlam." After an acquaintance of aristocrat Lord Mortimer dies in an attempt to escape from the asylum, apothecary general Master George Sims (played by Karloff, a fictionalized version of an infamous head physician at Bethlem, John Monro (physician)) appeases Mortimer by having his "Lunatic" put on a show for him. Mortified by the treatment of the patients, Mortimer's protégé Nell Bowen (Lee) first tries unsuccessfully to persuade Mortimer to help, then seeks the help of British Whig Party politician John Wilkes to reform the Psychiatric hospital, threatening Sim's corrupt practices. Mortimer and Sims conspire to commit Nell to the asylum, where her initial fears of the fellow inmates do not sway her sympathetic commitment to improving their conditions and she tends to the comfort of her fellow inmates. Alarmed by Bowen's imminent release following legal pressure by Wilkes, Sims plans to apply his most drastic "cure" to her but his attempt is thwarted by the inmates that Nell helped. Ultimately, Sims is deposed and Nell escapes and is reunited with her Quaker friend who had counselled her through the whole process.