Upon arriving at a hotel in Puerta Vallarta, Mexico, chronically unlucky Valerie Highsmith telephones her insurance magnate father to assure him of her safety. The conversation is interrupted as Valerie tumbles over the balcony and lands on the awning above the entrance. During a leisurely stroll through town, Valerie is knocked unconscious during a robbery. She awakens as criminal Frank Grimes attempts to removes her jewelry. When Valerie reveals that she has lost her memory, Frank takes her to Acapulco, Mexico, hoping to determine her identity and collect a ransom. Four weeks later, after Mr. Highsmith has lost hope of recovering his daughter, psychologist Dr. Julius Monosoff proposes a solution. He explains that people who suffer from “coincident misfortune syndrome” follow similar behavioral patterns, and recommends company accountant Eugene Proctor, Valerie’s male counterpart, as the ideal person to locate her. In desperation, Highsmith accepts the proposition, and teams Eugene with private investigator Raymond Campanella. Although Raymond is leading the search, Monosoff convinces Eugene that he is in charge, certain that the latter’s instinct for disaster will guide them to Valerie. As they embark on their journey, Raymond is both exasperated and amazed as Eugene cheerfully endures a head injury, threats from strangers, the loss of his wallet, and damage to his luggage. In Mexico, Eugene is admitted to the airport infirmary, where he learns that another American was admitted weeks earlier after walking into a door. Raymond produces a photograph of Valerie, and the nurse identifies her as the patient. After checking in to their hotel, Raymond discusses possible scenarios for Valerie’s disappearance, while Eugene is distracted by a flirtatious woman at the bar. The awkward encounter leads to a fistfight with the woman’s boyfriend, and another head injury for Eugene. Later, Police Inspector Segura informs Eugene and Raymond that Valerie was last seen with Frank Grimes, and refers them to a saloon where the criminal’s former girl friend is employed. As they enter the saloon, Eugene accepts a young woman’s invitation to dance, despite Raymond’s warning that she is a thief. Eugene refuses to listen, and is later beaten and robbed by the woman’s accomplices. He and Raymond locate the woman at a gambling club, run by her boyfriend, Fernando, and recover the money. When they discover Frank Grimes among the gamblers, Eugene and Raymond drive him to a secluded area for questioning. He admits to kidnapping Valerie, but claims he turned her over to Fernando after her medical bills exhausted his savings. A passing van, loaded with Fernando’s henchmen, unleashes a barrage of gunfire that kills Frank Grimes and disables the car. As they walk back to town, Raymond saves Eugene from quicksand, after which they are arrested and jailed for no apparent reason. Inspector Segura discovers his officers’ mistake and releases Raymond and Eugene. He informs them that Fernando has been arrested, and admits to sending Valerie to Mexico City, Mexico, as a precaution after Frank Grimes was abducted. However, her plane crashed in the jungle and no survivors were found. Raymond delivers the news to Mr. Highsmith, who believes his daughter is alive, and insists that the investigation continue. Raymond and Eugene fly to the crash site, but their trip is interrupted when Eugene has a severe allergic reaction to a bee sting. During his recovery in a field hospital, Eugene learns from a fellow patient about an American woman who inadvertently burned down an entire village while cooking breakfast. Raymond shows the man a photograph of Valerie and he screams in horror. After visiting the disaster site, Eugene and Raymond drive their Jeep to the edge of a canyon, where Raymond narrowly escapes falling to his death. Infuriated by his partner’s behavior, Raymond tells Eugene that he is merely an assistant, hired because he is plagued by the same terrible luck as Valerie. Eugene clumsily tries to attack Raymond, but runs headlong into the Jeep, pushing it into the canyon, and rendering himself unconscious. Raymond carries Eugene to the road and asks a farmer to drive them to a nearby mission. Eugene awakens in the infirmary and discovers Valerie in the adjacent bed. He takes her by the hand and they walk outside to a small pier on the riverbank. Although Eugene helps Valerie recover her memory, both are oblivious as a section of the pier breaks away and carries them toward a waterfall.