Dr. Richard Kimble (David Janssen) has been wrongfully convicted of murdering his wife in the town of Stafford, Indiana. The only clue to his innocence was a mysterious one-armed man (Bill Raisch) seen leaving Kimble's house right before he found his wife dead. On his way to death row at the Indiana State Penitentiary, the train wrecks and Kimball escapes. He then wanders the country searching for the mysterious one-armed man while working a series of menial jobs and trying to stay one step ahead of the authorities. Seemingly always in close pursuit of Kimball is Lt. Phillip Gerard (Barry Morse), the man responsible for his conviction who's now obssessed with his re-capture.

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