After a mishap in the classroom during his lesson on the evils of drugs and alcohol, Mr. Mackey, the school counselor, is fired. In an act of desperation, he turns to drugs and alcohol. Meanwhile, it's time for Ike's bris and, when Kyle and the boys find out what it means to be circumcised, they try to save Ike from that fate.
In this episode, Mr. Mackey gives a drug and alcohol prevention lecture entitled "drugs are bad", emphasizing the negative effects of smoking, drinking, marijuana and LSD, while the children not-so-subtlety make fun of Mr. Mackey's distinctive way of speaking (which goes right over the oblivious Mackey's head). The presentation is less than informative, consisting of the following format repeated for each subject: "Drugs are bad, you shouldn't do drugs." Mr. Mackey passes a sample of marijuana (he pronounces it Marriage-you-wanna) around the class so that the children can learn its smell and detect if their friends are smoking marijuana. Kyle, meanwhile, invites Stan, Kenny, and Cartman to Ike's bris, although he isn't completely sure what a bris is. Mr. Mackey then asks for the marijuana to be passed back to the front, but, alarmingly, it has disappeared. The children are then searched by the police, but the weed doesn't show up. Unfortunately for Mr. Mackey, this is interpreted to mean that the child who took it got away with it and Mr. Mackey is immediately fired by Principal Victoria. (It is then shown that Mr. Garrison is watching the Teletubbies at home while stoned).
After talking to Chef and checking with five other people, Stan rushes in and tells Kyle what (he believes) a bris is - a party to give Ike a "circumstision" and "chop off his wee-wee!". The boys are shocked. Kyle asks his parents what a bris is; they explain that it is "to celebrate your little brother's passage into life", and they are going to circumcise him - still misunderstanding, Kyle becomes extremely upset and begins plotting how to hide his brother from his parents until they return to normal.
Meanwhile, Mr. Mackey is harassed by passing drivers, and called a hippie, so he runs into a nearby bar to escape and ends up getting drunk. Back at his house, he discovers that the landlord has changed the locks because Mr. Mackey didn't pay the rent for days And he also heard Mr. Mackey was fired for selling drugs to children. Now Mr. Mackey has been evicted and homeless and sleeping in an alley, Mr. Mackey is given a spliff by a hobo, and sees the alley transform into a bright place with neon hues. The next day, Mr. Mackey meets two hippies in the woods and has some of their LSD, turning his head into a floating balloon - in this drug-addled state, he floats through the town.
To keep him away from his "wee-wee-chopping parents" prior to the bris, Kyle puts Ike on a train to Nebraska. Kyle makes an Ike-style doll, to try not to arouse his parents' suspicions, but this backfires when the doll is eaten by a dog, who is then run over by a truck in front of the Broflovskis' house. It is at the funeral that Kyle finds out that Ike is not his real brother, but was adopted from Canada. Upon discovering this, Kyle decides that Ike is not his "real brother" and he no longer cares about him; he then tells his parents that Ike is not really dead, but in Nebraska.
Mr. Mackey, now a hippie, meets a hippie woman and goes to fingerpaint at her house - before long, they decide to get married and have a honeymoon in India. Meanwhile, Kyle's parents make him come with them to Nebraska to find Ike - they discover him being used as a table-leg in a bar. When Kyle continues to refuse to treat Ike as his brother, he is grounded by his parents.
While on honeymoon, Mr. Mackey is captured by The A-Team, and his former employers say that they should have helped him with his drug problem rather than firing him. Mr. Mackey protests, saying that he likes his new life and that he actually hasn't done drugs since his first experimentation back in South Park. Nobody listens and in rehab at the Betty Ford Clinic, he is "cured" of his addiction to drugs.
The day of the bris arrives, and Kyle is still grounded and sulking in his room. Ike, catching on to Kyle's hard feelings towards him, tries to get through to Kyle's soft side by showing him family photos and wearing his distinctive green hat. When Dr. Schwartz arrives to perform the bris, Ike flees to Kyle's room in terror. Seeing Ike in distress prompts a change of heart in Kyle, and he defends his brother fiercely before it is explained to him what a circumcision actually is, "snipping the penis a little to make it look bigger", at which point Stan and Cartman decide they want to be circumcised too. Ike is circumcised and comes out okay, much to Kyle's relief.
The episode ends with Mr. Mackey telling the class again about the evils of drugs, with the children making fun of him again; all is back to "normal", or as normal as it ever gets in South Park.