The film commences in 1890 in the small town of Kings Row, focusing on five children. They are Parris Mitchell (Cummings), who lives with his French grandmother (Maria Ouspenskaya); Cassandra Tower (Field), daughter of Dr. Alexander Tower (Rains); the wealthy orphan Drake McHugh (Reagan); Louise Gordon (Nancy Coleman), daughter of the sadistic town physician Dr. Henry Gordon (Coburn), who performs operations without anesthetic; and the tomboy Randy Monaghan (Sheridan), whose father is a railroad worker.

Parris is attracted to Cassandra, whom the other children avoid because her family is “strange”: her mother is confined to the house and never seen. Dr. Tower takes Cassie out of school and Parris does not see her again until years later, when he begins his medical studies under Dr. Tower’s tutelage.

Parris’ best friend, Drake, intends to marry Louise despite the disapproval of her father. Louise, however, refuses to defy her parents and will not marry him. Parris and Cassie begin a secret romance, seeing each another at Drake’s house. At about this time, Parris’ grandmother becomes ill from terminal cancer and dies as he is about to go to Vienna for medical school. Parris, who decides to study psychiatry, proposes marriage to Cassie. She initially resists, running away, but later begs him to take her with him to Vienna. She then runs away again, back home.

The next day, Parris learns that Dr. Tower has poisoned Cassie and shot himself and has left his estate to him. He learns from Dr. Tower’s notebook that he killed Cassie because she was insane like her mother, to prevent Parris from ruining his life by marrying her, just as Tower’s life had been ruined by marrying her mother.

While Parris is in Vienna, Drake’s trust fund is stolen by a dishonest bank official. He is forced to work for the railroad and is accidentally crushed by a boxcar. The sadistic Dr. Gordon, who hates Drake, who he thinks is immoral, amputates both of his legs needlessly. Drake, who had been courting Randy before the accident, marries her and is now embittered and refuses to leave his bed. They commence a business, begun with Parris’ financial help, building houses for working families.

Parris returns to Kings Row and decides to remain there, when he learns that Dr. Gordon has died, leaving the town with no doctor. Louise reveals that her father amputated Drake’s legs because he thought it was his duty to punish wickedness. Parris at first wishes to withhold the truth from Drake and considers confining Louise to a mental institution, even though she is not insane, to prevent the truth from being revealed to Drake and other victims of her father. But instead, persuaded by his new friend, Elise (Kaaren Verne), he tells Drake what happened. Drake reacts with defiance and summons a renewed will to live instead of the deep clinical depression Parris had feared. Parris is now free to marry Elise, having helped his old friend return to a productive life.

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