A pair of musicians are performing their act when one of them is almost electrocuted. Mannix is hired to look into the matter. But the detective faces twists almost immediately. For starters, the woman who hired Mannix isn't who she said she was. Mannix also needs to act fast before another attempt on the musician's life is made.
Joe Mannix receives an urgent phone call from his friend George Lassiter asking him to come to Albuquerque because of a problem with Lassiter's daughter Jeannie, who is also Joe's goddaughter. Mannix arrives quickly only to be told that the problem has been solved. Sensing that he's not receiving the whole story, though, Mannix decides to conduct his own investigation -- leading him to discover that his friend is involved in a novel form both of kidnapping and of paying the ransom.
Jenny Cole, the daughter of a friend of Joe Mannix, awakens after almost a year in a coma following a hit-and-run accident. But the celebration of her return to health is soon cut short when someone tries to kill Jenny. This leads Mannix to conclude that Jenny must have seen something on the day of the accident that she shouldn't have seen -- and that someone wants to tie up that loose end by "putting her to sleep" permanently.
Someone has been calling Joe Mannix with vague threats of harm, and he initially disregards them as an occupational hazard. But when the threats turn into a near-fatal attack, Mannix reviews his old cases for a clue to the person's identity - and thinks he may have found it in an old extortion case in which he sent the extortionist to prison.
After spending three weeks incommunicado on a fishing trip, Mannix returns to Los Angeles to learn that his buddy from the Korean War, Harry Endicott, has apparently been killed in a plane crash. Finding a letter from Endicott appealing for help that was mailed the day before the crash, Mannix decides to run down some leads in Endicott's hometown of San Francisco. But upon his arrival, Mannix finds the mystery much deeper than he suspected - when first several people claim to have seen Mannix in the past few days, and then he locates an apartment where everything ...
Joe Mannix is visited by Japanese detective Tami Okada (whose first name is pronounced as if spelled "Tommy"). Searching for a missing Japanese government courier who was apparently kidnapped upon arrival in Los Angeles, Okada asks Mannix for help. Mannix agrees, escorting Okada to the Japanese Village in Buena Park, and to "Little Tokyo" -- but their investigation soon leads to suspicions that the courier's disappearance may have been staged.
Joe Mannix is confronted by Harry Bennett, with whom Mannix served in Korea and who was later court-martialed, on testimony from Mannix, for giving information to his captors while a prisoner of war. Bennett claims that he is going to put Mannix through the same ordeal he faced at the hands of the North Koreans, and gives Mannix a name that Bennett claims Mannix will be unable to hold back once he becomes a captive. Then Bennett's threats seem to come true when Mannix is offered a sizable sum of money for the name of an informant within an underworld organization - ...
Peggy's cousin and her husband, a Vietnam veteran named Bill Rogell, are traveling to Los Angeles by bus when Rogell runs into fellow veteran Clint Williams at a stopover. While they reminisce, Rogell thinks he recognizes another man from their unit, but Williams insists Rogell is mistaken. Joe Mannix becomes involved, however, when the couple arrive in Los Angeles and Rogell is stabbed at the bus station.
At the start of a long weekend, off to a fishing vacation with friend Tony Elliott, Mannix stops at Tonys office so Tony can pick up a set of fishing flies. They walk in on a methodical heist of the businesses in the building. Mannix is trapped in the building, playing a cat and mouse game with the three burglars.
While driving back to Los Angeles, Mannix gives a lift to a black hitchhiker named Perry Riggs. Riggs is soon arrested at a roadblock, however, and charged with the murder of his former boss, a scientist who had been working on a formula for a gasoline replacement. Mannix decides to stay in the town to investigate the circumstances of the man's death -- in the hope that he can find evidence exonerating Riggs.
Mannix travels to an island that's part of a South American country. Mannix's client wants to repay the man for the saving the life of the son of the client some years earlier. But Mannix soon discovers the case is more complicated than he bargained for. The man he's searching for is part of a plot to assassinate the president of the country. Just as Mannix is putting the pieces together, he's captured by the conspirators.
The conspirators assassinate the president of a South American country and successfully frame Mannix for the killing. Now, the detective must dodge the authorities and hunt the conspirators as he tries to clear his name.
Newspaper publisher Darrell Bigelow has political ambitions, but is concerned about the extramarital activities of his wife, Rebekah. Bigelow hires Joe Mannix to "bring her home," and Mannix is soon able to track her down. But his easy success in closing the case soon leads Mannix to suspect that Bigelow's story was a cover-up, and that he used Mannix for a different, and much darker, purpose.
A hit man shoots his victim, a notorious crime boss, from a sniper's perch, but moments later can find no body where the man fell. Unable to convince the men who hired him that the crime boss is actually dead, he concocts a story about being a witness to a shooting and hires Joe Mannix to investigate whether a man really was killed that night, and if not, what happened to him.
In the series' final show: To ensure a safe release of 6 hostages taken by a desperate drug dealer, Mannix, with no other choice, must find and deliver a member who turned informer against the dealer and his men.