An overly upbeat anti-smoking group called Butt Out!, which incorporates elements of dance and hip-hop into its routine, performs at South Park Elementary, which brings out a mixture of boredom, annoyance, confusion, and fear in the boys. At the end, Butt Out! enthusiastically calls out "If you don't smoke, you can grow up to be JUST LIKE US!"
The boys, not wanting to be anything like Butt Out!, take up smoking that afternoon. When caught by Mr. Mackey, they discard their still-lit cigarettes into a nearby dumpster, which ignites and proceeds to burn the whole school down. Their parents all come into the burned down school. When Principal Victoria tells the parents about them smoking, Sharon tries to convince herself that Stan isn't a filthy smoker and Randy is close to disowning him. Liane grounds Cartman for three weeks, saying that smoking tops every horrible action he ever did. However, Sheila blames it on the tobacco companies brainwashing them. The other parents follow suit, and the boys are happy to transfer the blame in order to avoid being grounded for three weeks, although Kyle, recognizing the classic pattern of a South Park story line, foresees it getting out of hand.
The town then calls in Rob Reiner, and his group known as Rob Reiner's Smoke Stoppers, in order to combat the spread of smoking among children in South Park. Despite the fact that Reiner is against smoking, he is obese and eats large amounts of junk food on an almost constant basis (another unhealthy pursuit). Even when he's giving a speech about how harmful smoking is to your body, he crams food into his mouth. He is instantly loved by Cartman because "He just goes around imposing his will on other people; he's my idol." The rest of the boys are suspicious of him as he attempts to use them in order to get Colorado to pass a ban on smoking in public.
Reiner, disguised as a woman named "Rita Poon," gets a tobacco company to give them a tour around a factory near South Park. Reiner hopes to sabotage the company by taking the boys there and then taking a picture of them inside and photoshopping it ("You've just been Reiner'd!"). The tobacco company reveals how important the industry has been to the country as a whole, the workers are really nice and everybody employed there looks really happy and friendly; they appear to be perfectly aware of the dangers of smoking but allow people to have the freedom to smoke. By contrast, Reiner's anti-smoking group is a group of Boris-and Natasha-style madmen who speak in Peter Lorre-esque voices and act similar to vampires.
Feeling they need to push their agenda further, Reiner asks for one of the boys to appear in an anti-smoking commercial in which he says he is dying of second hand smoke. While Stan, Kyle and Kenny want nothing more to do with Reiner and his group, Cartman is excited at the chance, and assumes the other boys are as well. After making the commercial, Cartman is confused by how his dialogue says he will die. He is then offered a poisoned green cupcake by one of Reiner's associates, while Reiner tells Cartman that he needs to sacrifice himself for the sake of the Anti-smoking movement. Fearful, Cartman escapes, and seeks the help of Stan, Kyle, and Kenny, who after much convincing, agree to help him.
Eventually, as Kyle predicted, they end up back at the cigarette factory where the townspeople, bearing torches, demand the factory to release them. Reiner reveals his plan to the townspeople that he does indeed plan to kill Cartman, at which point the boys call him "Fat Facist", and at which the townspeople turn against Reiner. Stan confesses to everyone that they smoked on their own free will but Reiner still wants to take down Tobacco Companys, telling them not to mess with anti-smoking groups. Cartman, who lost all faith on Reiner, stabs him with a fork causing mass amounts of goo to come out of him, killing him. Hearing that the boys admit that they had smoked on their own free will, Sheila grounds Kyle, followed by Liane grounding Cartman. Stan says that they learned their lesson but Kyle, who foresaw the events, says they never learned anything (this part is added sometime after the initial broadcast).