Nick feigns illness to avoid going with his grandfather, who leaves but not before inadvertently swallowing his mini-relatives -- van and all. Nick interprets Wayne's help message in the newspaper and, realizing what has happened, rushes to his family's aid. It's a race against the clock as the tiny Szalinskis travel on a "fantastic voyage" through Grandpa's body, seeking a way out before the shrinking effect wears off in three hours.

After their home is burglarized, Wayne becomes overly concerned for the safety of his family and invents a home security system for their total protection. F.R.A.N., the Felon Repeller & Accident Neutralizer (patent pending), takes her duties very seriously and involves herself in every facet of the household, from protecting Amy from bad fashion choices to preventing Wayne from eating too much rich pie. Diane is wary of the overprotective computer, not realizing that F.R.A.N. has developed a mind of her own.

Afraid of ending up a four-eyed math monkey like his dad, Nick tests out Wayne's new invention -- the Szalinski Retina-Rotator (patent pending), turning the controls up to 150 percent. Nick's enhanced vision allows him to perceive invisible wave lengths on the electromagnetic spectrum; in other words, he can see ghosts. He befriends the spirit of a dead 1930s gangster named Louie "the Loon" Matagrano who died robbing the Matheson Federal Bank. Louie helps Nick develop a tough reputation at school by ghost-merging with him and punching out the school bully.

Amy develops a crush on Mr. O'Donnell, her handsome 37-year-old history teacher. She uses Wayne's time-travel machine to transport herself to 1976 where she hopes to meet up with the teenage version of Mr. O'Donnell and make some history of her own. Wayne travels back in time to rescue his daughter, but the Szalinski Time Hopper (patent pending) malfunctions and the two are stuck in the past. With some help from a romantic memory, Diane and Nick repair the machine -- just in time -- and the Szalinskis are reunited in the present.

Wayne suffers an attack of jealousy when Nick invites Wayne's younger brother, TV scientist Randy Rude the Science Dude, to speak at the school Science Club assembly. At the last minute, Wayne decides to bring along the shrink ray for a little demonstration of his own, but he accidentally shrinks Randy, the shrink ray and himself. The tiny brothers Szalinski end up as prizes in a McDonald's Happy Meal. As Diane and the kids literally dismantle the McDonald's looking for an address, Wayne and Randy escape Play Doh, cha-cha with a chameleon and put aside their sibling rivalry, before they finally get big again.

Even though it means jeopardizing his success with Jennings Labs, Wayne decides to shelve his virtual reality device when he realizes there might be ethical and criminal problems associated with brain-swapping. Diane has work problems, too -- the Addams brief is due in the morning and Quark ate her only copy. When trying to access her back-up file on a computer disk, Diane mistakes the Szalinski Neuron Nudger (patent pending) for a lap-top computer and accidentally exchanges brains with a supercilious cat named Persephone.