The story begins with Theodore Roosevelt's funeral. The narrator, a reporter with the New York Times, decides to tell a story that happened more than 20 years earlier in 1896 when Roosevelt was Police Commissioner of New York City. A serial killer is murdering young male prostitutes.

Roosevelt invites the infamous Dr. Laszlo Kreizler to form a special unit to track down the killer. The unit also includes the narrator and three members of the police department. Kreizler's qualification is that he is an alienist who champions the radical new concept of forensic psychiatry: the belief that one can predict a criminal's behavior by reconstructing his personality based on evidence in the crimes themselves. This concept smacks of determinism. Thus, Kreizler was violently opposed by many, including the religious establishment, who believed Kreizler was denying that people were morally responsible for their crimes.

Because of the sensitivity of their mission, the small investigative unit operates secretly, but runs into powerful opposition. Over several months Kreizler and his colleagues perform the seemingly impossible job of identifying and tracking down the killer, using Kreizler's psychological methods.