Dr Miles Bennell returns his small town practice to find several of his patients suffering the paranoid delusion that their friends or relatives are impostors. He is initially skeptical, especially when the alleged dopplegängers are able to answer detailed questions about their victim's lives, but he is eventually persuaded that something odd has happened and determines to find out what is causing this phenomenon. This film can be seen as a paranoid 1950s warning against those Damn Commies or, conversely, as a metaphor for the tyranny of McCarthyism (or the totalitarian system of Your Choice) and has a pro- and epilogue that was forced upon Siegel by the studio to lighten the tone.

Detective Virgil Tibbs is caught up in the racial tension of the US South when he is arrested after the murder of a prominent businessman. Tibbs was simply waiting for his next train at the station in Sparta, Mississippi and the confusion is soon resolved but when local police chief Gillespie learns that Tibbs is the Philadelphia PD's number one homicide expert, he reluctantly asks for his assistance. The murdered man, Mr. Colbert, had come to Sparta from the North to build a new factory and his wife and business associates immediately point the finger at Endicott, the most powerful man in the county and the one who had the most to lose if a major new employer comes to the area. Tibbs' life is clearly in danger but he perseveres in a highly charged and racially explosive environment until the killer is found.