International spies Napoleon Solo and Illya Kuryakin travel around the globe in an effort to track down a secret formula that was divided into four parts and left by a dying scientist with his four of five daughters, all of whom live in different countries. His widow, Amanda, is murdered at the beginning by the counter-spies of the organization THRUSH. Evil THRUSH agent Randolph also wants the formula, and is aided by his karate-chopping henchmen.

Hounded by the press for shooting a doctor, an ousted Los Angeles policeman works his own case.

Lt. Col. George Armstrong Custer has been reinstated and assigned to command the 7th Cavalry Regiment at Fort Hays. The regiment has become a ragtag outfit of thieves and ruffians and Custer must whip the soldiers into shape to fight, the Kiowa, Sioux and Blackfoot tribes who confront them. These tribes are being supplied shotguns by a white gunrunner and Custer and his men must rescue General Terry and the Fifth Cavalry Regiment from annihilation when they are ambushed and trapped by a large Kiowa war party.

Matt Helm is called out of retirement to stop the evil Big O organization who plan to explode an atomic bomb over Alamagordo, NM, and start WW III.