In Alaska, agents of a reborn Thrush steal nuclear devices from a U.S. plane. Janus (Geoffrey Lewis), a traitorous UNCLE agent hired by the new Thrush, declares the criminal organization "has come of age" because it is now "a nuclear power." Shortly thereafter, the former Thrush leader Justin Sepheran (Anthony Zerbe) is sprung from a minimum-security prison (he had been considered a model prisoner). Thrush has set up a new HQ in Libya and is demanding $350 million in ransom. Just for fun, Thrush demands former UNCLE agent NS deliver the ransom. Current ace UNCLE enforcement agent Benjamin Kowalski (Tom Mason) is not amused. "Who is this guy?!" Kowalski utters upon hearing that Thrush wants Solo to deliver the ransom.
NS, now a well-to-businessman, is gambling in Las Vegas with some Russian officials overseeing a ballet company on tour. Luckily, he still carries his pen communicator when the summons comes from Sir John Raleigh (Patrick Macnee), the new head of UNCLE. It is implied that Alexander Waverly has only recently died and Raleigh clearly is shown to have just arrived at the NYC HQs. NS, who is losing a high stakes poker game, agrees to help -- especially after UNCLE offers to bail him out financially. But NS also has to cope with a Russian ballerina, Andrea Markovich (Gayle Hunicutt) who wants to defect. A wild chase ensues, with NS chased by the KGB. Visiting British agent "JB" (one-time 007 George Lazenby) helps out with his especially equipped Aston Marton DB V.
In New York, the situation is explained to NS. He says he needs IK's help. But IK, now a dress designer, quit UNCLE also -- he was the agent betrayed by Janus. Eventually, the duo is briefly reunited before working opposite ends of the case. IK trails Thrush officials to Chicago while NS guards an innocent actor, Nigel Pennington-Smythe (Simon Williams) whose uncle designed the weapon. Pennington-Smythe, conveniently, has a photographic memory and that could assist Thrush. Pennington-Smythe, of course, is kidnapped by Thrush in New York.
Solo has a rough time. Kowalski pokes fun at him and Andrea is working for Thrush -- although she's been blackmailed into doing so. Solo figures out only Andrea could have tipped off Thrush to Solo's plans for protecting Pennington-Smythe. NS confronts Andrea but is knocked out by Guido, Sepheran's favorite thug. Solo meets Sepheran in Libya to discuss details of the ransom drop. But Solo concludes Sepheran will detonate the bombs anyway. Kuryakin isn't doing so well either. He's captured and is in a cavern near a nuclear power plant, where the bomb is ticking away.
Eventually, NS leads an UNCLE task force against the new Thrush HQs in Libya while IK defeats Janus. The traitor actually was going to double cross Thrush (well, whaddya expect from a guy named Janus?), deactivate the bomb and sell it to the highest bidder. Kuryakin and Janus fight and IK dispatches the villain. Now it's up to Pennington-Smythe to deactivate the bomb. He does so but not before the now-familiar scene where it's down to cutting one of two wires and the hero has to guess. Meanwhile, the UNCLE raiding party has defeated the Thrushmen and Solo rescues Andrea. Sepheran tries to detonate the bomb but is too late -- Pennington-Smythe guessed correctly and the bomb is deactivated. Solo confronts Sepheran but the Thrush leader shoots Solo and escapes. However, Solo evidently was hit in the "fleshy part of the shoulder" to use Kitt Kittridge's words (see MFU Eps. 21) and Solo isn't hurt too badly. Also conveniently, the cavern has a closed-circuit TV connection to Thrush HQs in Libya. This enables Solo and Kuryakin to compare notes (which is nice since, by this time, they haven't talked to one another for nearly an hour of screen time). "I think was a lot easier 15 years ago," Solo says. "It was," agrees Kuryakin, as ever a man of few words.
Despite the pain (and Solo isn't even wearing a sling -- it must have been a superficial wound), our duo meet at a bar and ponder whether they were better off working for UNCLE. Afterall, Kuryakin muses, things are much clearer when somebody is shooting at you. Just then, there's a news bulletin about how the U.S. secretary of state is missing. Suddenly, Solo and Kuryakin get another call from Sir John......