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At California's San Quentin Prison, rioting and other problems prompt the board of directors to fire the prison's top management and ask bookkeeper Clinton T. Duffy, a second-generation employee, to take over as warden for thirty days until a replacement can be named. With the encouragement of his wife Gladys, Duffy, who is dedicated to the prison and its men, accepts the position and immediately implements changes, such as better food. He abolishes solitary confinement and, to lessen the climate of betrayal and distrust, refuses to listen to information supplied by established stool pigeons, who inform on their fellow prisoners in return for favors. After forbidding abuse of the prisoners, Duffy fires the guards known for their inhumane treatment. Due to a contractual agreement, Duffy must give two months notice of dismissal to the cruel and corrupt guard captain, Pierson, who takes revenge by reporting Duffy's new practices to the prison's board of directors, hoping to get him removed. However, one of the directors, Boyd, stands behind Duffy, and Pierson is eventually terminated. Meanwhile, Edward "Romeo" Harper, a prisoner considered to be a troublemaker, is released from solitary confinement. The well-educated Romeo intrigues Duffy, as he seems too intelligent to have attempted to break the basic prison rules for which he is being punished. Although Pierson had claimed that Romeo was caught carving a knife out of a wooden toothbrush handle, Romeo claims he was carving a ring. To gain his trust, Duffy gives Romeo a knife and several toothbrush handles and later, Romeo presents Duffy with a wooden ring. Duffy's refusal to listen to informers makes him vulnerable to the impending breakout he knows is being planned by a small group of prisoners. Although Boyd warns him that he will lose his job if the escape succeeds, Duffy refuses to risk showing favoritism by changing his new policies. The break is attempted, but is quickly thwarted by Romeo and other prisoners who appreciate the improvements brought about during Duffy's tenure. Later, Romeo is assigned to work in the infirmary with three other prisoners. With Gladys' help, Duffy hires a female nurse, Anne Halsey, to take charge of the medical ward, as part of his reforms to build the men's morale. After her first attempts fail to gain the respect and trust of her subordinates, she nearly quits. However, she wins them over one by one, except for Romeo, who was betrayed by own his wife. Confused by his conflicting attraction for Anne and his distrust of all females, Romeo gets drunk while on night duty and gives the wrong injection to a patient. After inadvertently discovering Romeo's feelings for her, Anne takes responsibility for the incident and agrees to resign. The next day, the recovered Romeo learns about Anne's dismissal and confesses. Duffy, who watches from his window as Romeo convinces Anne to return to duty, realizes that Anne has been hiding her true feelings about Romeo. Later, Winant, the corrupt prosecutor who put Romeo and others unjustly behind bars, is convicted of bribing a witness and sentenced to time in the prison. To house Winant with the men he wronged would put his life in jeopardy, and Boyd warns Duffy that his job is in peril if anything happens to the lawyer. At first the arrogant Winant, who is planning his appeal, demands special treatment and flaunts his many political connections, confident that Duffy must ensure his physical safety. However, Duffy sees that the men interpret Winant's special protection as favoritism, and decides to stand on his principles. He assigns Romeo as Winant's cell-mate and bodyguard, which is risky, because Winant forced key witnesses to leave town in order to win Romeo's conviction, and Romeo has openly vowed revenge. When several prisoners plan Winant's assassination, Duffy senses the impending murder and alerts the guards. Anne rushes to Romeo's cell, admits that she loves him, and convinces him to stop the killing, so that he will someday be free and they can be together. Romeo then proceeds to where the prisoners have cornered the frightened Winant and fights to protect him. Although injured, Romeo manages to stall the would-be murderers until the guards arrive. Presuming that Romeo is part of the ambush, Duffy prepares to punish him, but Winant, reformed by Romeo's willingness to rescue him, speaks up and admits that Romeo saved his life. Wanting to right the wrongs he has committed, Winant asks Duffy for permission to set up a law office in the prison. Although Winant loses his own chance for an appeal of his case, by admitting his crimes against Romeo, he wins an acquittal for Romeo, who then marries Anne. Watching Romeo and Anne leave together, Duffy muses that, ironically, it is he who will never leave San Quentin.