The Finsters are visiting Chas's parents, the DeVilles are staying with Betty's brother Freddy, Tommy, Dil and his parents are at the beach, and Angelica and her parents are on a business trip, when a broadcast comes on about a serious flu epidemic called the Gray Plague that can be fatal to small children. Tommy meets a sickly homeless boy named Chongo and the kids have to go home early to get vaccinated. However, there is a limited amount of shots and Tommy ends up not getting vaccinated.
The next day, the kids visit with Tommy and Taffy takes them to the park, but Tommy seems out of sorts. He gets pushed into mud by a mean boy and they go to the Finsters' early, where Angelica throws the Reptar doll onto the roof of the tree house. While trying to fetch the toy, Tommy falls and is knocked out, then the adults discover that he is sick. Stu and Didi take their boys home, but at night, he has trouble breathing and is taken to hospital where they discover that Tommy does have the gray plague.
The babies look for Tommy and find that he's in the hospital. They make get well cards and sneak into an ambulance to visit Tommy. They reach the hospital and try unsuccessfully to take a weak, sickly Tommy home.
Tommy gets invited to Chuckie's third birthday party and takes medicine, but in a nightmare, an anthropomorphic version of the plague tells him that the medicine has horrible side effects.
Turns out that the side effects are just a bit of sleepiness and irritability and Tommy gets his appetite back and loses most of his cough, so he is able to go to the birthday party but must keep taking the medicine. Before the party, they meet a cheerful boy named Zachary, aka Zack, and his aunty Celeste. Zack likes Chuckie and Kimi but thinks Tommy is "depressed" (due to the medicine's effects making him gloomy) and Phil and Lil are "disgusting". He shows up at the party, but Tommy is asleep and can't go, so Zack asks to be Chuckie's new best friend.
Then, Betty and Kira argue. Phil and Lil tell Tommy this and think this means that the Finsters aren't their friends anymore, which makes Tommy cry but the adults think it's just the medicine. They then go to Reptar live but Tommy has trouble bonding with Zack and misses it due to falling asleep. He decides he's had enough of being out of sorts and wants to stop taking medicine (which is also partly due to a dream he had where Reptar told him not to take it).
Then, Tommy gets mad and argues with the babies and has a dream that changes his mind about taking the medicine but pours it down the sink. The next day, Tommy makes up with Chuckie and Kimi and makes friends with Zack and Tommy and Chuckie go to the basement to retrieve the screwdriver while Kimi, Angelica and Zack play fashion show, but Tommy gets sick again. Stu tries to help but accidentally drops Dil and makes him bleed. This makes Didi mad at Stu and they decide to get a divorce. Dil gets stitches and he is fortunately not brain-damaged, but Tommy's only chance is to wait for the vaccinations again.
Didi lives in an apartment with her sons, Phil and Lil turn two, Betty wants Stu and Didi to be back together and she and Kira have made up, but Tommy has lost his spirit of adventure. Tommy turns two and goes to the movies and then he gets a vaccination, goes back to normal and his parents get back together.
