Middle-aged middle-manager Jim Fry, with the same company for fifteen years, is in a comfortable rut. But life becomes less predictable when he doesn't receive an invitation to an important luncheon being held by the new company president. Convinced that he's about to lose his job, Jim begins to mull over his limited prospects when his wife confirms that she's pregnant.

Former radio singer Kay learns from her gossipy friends that her husband, Steve, has had an affair with chorus girl Crystal. Devastated, Kay tries to ignore the information, but when Crystal performs one of her musical numbers at a charity benefit, she breaks down and goes to Reno to file for divorce. However, when she hears that gold-digging Crystal is making Steve unhappy, Kay resolves to get her husband back. The Opposite Sex is a remake of the 1939 comedy The Women.

Told in flashback form, the film traces the rise and fall of a tough, ambitious Hollywood producer, Jonathan Shields, as seen through the eyes of various acquaintances, including a writer, James Lee Bartlow; a star, Georgia Lorrison; and a director, Fred Amiel. He is a hard-driving, ambitious man who ruthlessly uses everyone on the way to becoming one of Hollywood's top movie makers.

The drought-plagued ranchers of Sundown have to market their cattle at a loss in order to meet mortgage payments held by banker Cylus Cuttler. Then, Sheriff Tex Rockett is forced to quarantine all the cattle on the local ranches because of a hoof-and-mouth disease outbreak. Steve Davis herds his cattle to the railhead anyway, and Tex is forced to arrest him. Urged on by the banker's son, Nick Cuttler, the angry ranchers storm the jail, but Steve's sister Bee persuades them to await the trial. Steve, with Nick's help, breaks jail and is told he must kill Tex to aid the ranchers. Meanwhile, government man Bret Stockton and Tex see Nick and his men treating cattle in an unusual way. Tex finally proves that the Cuttlers have been treating the cattle with acid to give a false impression of the hoof-and-mouth disease.