The story picks up 15 years after the original shipwreck. Gilligan has a nightmare about the island melting. The film then notes that far away from Gilligan's Island in an unidentified country (one may assume the U.S.S.R.), a military unit is monitoring a satellite that is experiencing technical problems. The scientists controlling the satellite activate a self-destruct mechanism to prevent the satellite from crashing to Earth, as it contains a disc that holds some very important, top-secret information. The metal disc from the satellite is not destroyed, instead making it through the Earth's atmosphere and landing at the lagoon, eventually being found by Gilligan.
The movie picks up directly after the end of Rescue from Gilligan's Island. The castaways are once again stranded on the same island that they had been on for so many years. The storm has contaminated all of the underground springs, and they are desperately searching for fresh water. Gilligan stumbles upon a couple of planes that are hidden in the jungle that they had somehow never noticed before during their fifteen years on the island. It is revealed that the island was a base of operations for the Army Air Corps during World War II, and the hangar was abandoned and overgrown by jungle brush. The tidal wave destroyed the foliage and exposed the hangar. The Professor believes that he can combine the two planes into one and fly them all back to civilization. He succeeds in cobbling together an airworthy plane and, dubbing it Minnow III, they head back. This occurs despite the fact that in two different episodes of the original series, it was established that the Professor cannot fly a plane.
The former castaways own and operate a vacation resort on the formerly-deserted island, called "The Castaways", which was introduced in the previous film, The Castaways on Gilligan's Island. The Harlem Globetrotters, a traveling troupe of merry basketball players, are on a plane ride over the Pacific Ocean when it has engine trouble and they are forced into an emergency landing onto Gilligan's Island. After a brief time struggling in the jungle, they are discovered by Gilligan and Skipper and welcomed to "The Castaways." Meanwhile, J.J. Pierson, a corporate raider and the worst business rival of Thurston Howell III, has a plan to bamboozle the owners of The Castaways (Gilligan and his friends) into signing over ownership to him, as the island contains "supremium", an ore which provides large sources of energy. Eventually Gilligan and the Skipper uncover the conspiracy, with Pierson agreeing to tear up the fraudulent contracts if the Globetrotters play his team, the New Invincibles, which is a team of robot players. Notable sports broadcasters Chick Hearn and Stu Nahan appear as part of the basketball game scene, with Hearn calling the play-by-play action of the climactic showdown. The Globetrotters have no idea how to defeat a team of robots, until Gilligan unknowingly says they have not done any of their fancy tricks, causing the Professor to give a halftime pep talk to the Globetrotters that the New Invincibles would be caught off-guard. The Globetrotters start scoring against the New Invincibles, but when injuries sideline a couple of the players, Gilligan and Skipper must serve as substitute Globetrotters.
Society breaks down after a virus causes the infected to turn into cannibalistic killers. When Evie's husband John becomes separated from the rest of the group during an attack, the survivors fall back to their emergency shelter. Gary and Evie want to wait for John, as they all agreed they would do in such a circumstance, but Bob becomes increasingly impatient. Citing the realities of the situation, Bob says they must assume John is dead and leave for a more permanent shelter. Although Bob backs down, he later takes the group's car, rifle, and supplies by force. When Gary objects, Bob kills him. Sammy, the group's mechanic, and Marge, Bob's wife, leave with him; Evie stays behind by herself to wait for John.
A group of college students break into an abandoned school to explore it. Once inside, they find that the school is not completely abandoned thanks to a eugenics program gone horribly wrong.
Starflight, the first hypersonic transport is being prepared for a media-covered inaugural flight from Los Angeles to Sydney, Australia, a planned two-hour flight. The passengers bring some of their problems on board: the pilot, Cody Briggs (Lee Majors), is unfaithful to his wife Janet (Tess Harper) and having an affair with the media relations representative for Thornwall Aviation, Erica Hansen (Lauren Hutton). Hal Parisi (Phil Coccoioletti) married another passenger because she won the trip on TV, but he is only interested in getting his stolen gold out of the country. Freddie Barrett (Terry Kiser) is trying to get his communications satellite launched from Australia to start his business carrying television signals. Starflight’s takeoff is delayed a short time so that the deceased Australian ambassador and his wife, Mrs. Winfield, can be taken aboard. Del (Kirk Scott), the first officer, remembers that nothing good happened the last time a corpse came aboard his aircraft. Finally, Josh Gilliam, the designer (Hal Linden), has misgivings, wishing the engines were under ground control.
In February 1988, two pilots in a flight simulator face the challenge of landing a crippled jet that experiences a cabin decompression, an engine fire and a loss of hydraulics. The three emergency situations foreshadow the events of Paradise Airlines Flight 243, taking place two months later.
At a government laboratory in rural California, a weaponized version of influenza (called Project Blue) is accidentally released, immediately wiping out everyone on staff except for military policeman Charles Campion and his family, who flee the base. However, Campion is already infected by the superflu, nicknamed "Captain Trips", and spreads it to the outside world. That evening, Campion crashes his car at a gas station in East Texas where Stu Redman (Gary Sinise) and some friends have gathered. When they investigate, they find Campion dying of the flu next to his wife and baby daughter, who are already dead. Campion tells Stu with his dying breath that he was followed from the base by a mysterious figure, and states "You can't outrun the Dark Man". The next day, the U.S. military arrive to quarantine the town. While the other townspeople quickly become ill and die, Stu remains healthy and is confined at a CDC facility in Vermont order to study a possible cure. This proves futile and the superflu rages unchecked, causing civilization to collapse and killing over 99% of the population of the entire world in less than two months.
The story begins in the mountains of Bavaria, Germany, where wildlife documentarian Ernest Helms (Michael Winters) is filming local wildlife. While filming, he discovers a man attempting to break into his rental car. After foiling the man's attempt, Helms prepares to drive away but is thwarted by the man smashing the driver's window. Helms, however, succeeds in escaping the crazed man, but receives a minor cut on his hand. A few days later, in Frankfurt, Germany, Captain James Holland (Richard Dean Anderson), amidst preparations for his forthcoming transatlantic flight as Captain of Quantum Airlines Flight 66, is told by his doctor he does not have cancer. On board Flight 66, a Boeing 747, Helms (already displaying signs of illness) is assisted to his seat by flight attendant Brenda Hopkins (Kate Hodge). Shortly after takeoff, Helms rises from his seat and falls into cardiac arrest, and Brenda gives him CPR. Head flight attendant Barb Rollins (Jennifer Savidge) notifies Holland of the emergency, and the Captain and his check pilot, Daniel Robb (Richard Lawson) set a course for London's Heathrow Airport,. However they are turned away when British Air-Traffic Control informs them that one of the passengers (Helms) could be infected with a deadly strain of influenza.
Following a global economic collapse resulting in a post apocalyptic world, Matti (Kelsey Hutton) and her older sister Joslyn (Eve Kozikowski) are hiding beneath the floor as an armed intruder searches their house. After finding their parents killed, Matti plans on traveling to their grandmother's house, taking a shotgun and five shells she found scattered near her father's body. Maddi uses one shell for target practice before leaving the home. The sisters travel, staying in abandoned places and almost drown crossing a river. Maddi begins having recurrent dreams involving a yellow brick road and other imagery from The Wizard of Oz, whose original book she often reads to her sister.
While Dori Thorell (Sharon Lawrence) and her 9-year-old son, Danny (Michal Suchánek), eat breakfast, Sam Thorell (Garwin Sanford) calls from his business trip. Ballerina Diane Agostini (Jennifer Garner) is on the phone with her father when a blender shakes off the counter. Dismissing it, she ends the call and rushes off to a rehearsal session at the New York City Ballet. But she's scolded for being late. Public defender Evie Lincoln (Lisa Nicole Carson) talks with her client Joshua Bingham (JR Bourne) about his case. That evening, tremors cause a gas leak at Diane's apartment complex. Though the electricity is still on in the evacuated building, Fire Chief Thomas Ahearn (Tom Skerritt) sends his crew inside. The building explodes, killing several men. At a party at Gracie Mansion, Evie's grandmother Emily Lincoln (Cicely Tyson) chastises her for being late. Her father, Mayor Bruce Lincoln (Charles S. Dutton), coerces her into going to a job interview at a big law firm.
During the Cuban Missile Crisis, a Russian sub is sunk while en route to Havana. As the sub goes down, the hold is breached and barrels full of some mysterious substance tumble out. Years later, an American nuclear submarine is transporting a captured terrorist to the States. The terrorist's henchmen, however, are planning to hijack the sub and rescue their leader. Meanwhile, a large mutated octopus is approaching the sub at high speed.
The USS Charleston (SSN-704), a 688i variant Los Angeles-class submarine, is equipped with a caterpillar drive and is on station following a nuclear exchange, and is under the command of Captain Dwight Towers.