17-year-old Telly (Leo Fitzpatrick) and a 12-year-old girl are kissing. Telly convinces the girl, who is a virgin, to have sex with him. Afterwards, he meets his friend Casper (Justin Pierce). Telly tells Casper about his sexual experience in graphic terms. They go inside a local store, and Casper shoplifts malt liquor as Telly distracts the cashier. They then steal a peach, using the same set-up just outside the store from a sidewalk display. Looking for drugs and food, they head to their friend Paul's apartment, though they express dislike of him on the way there. They arrive at Paul's house, inhale nitrous oxide out of balloons, talk about sex, and smoke marijuana while skating videos play on TV. The scene intercuts with a group of girls, among them Ruby (Rosario Dawson) and Jennie (Chlo Sevigny), talking about sex and contradicting what the boys say, especially about oral sex.
Ruby and Jennie mention that they were recently tested for STDs at Ruby's request. Ruby's test is negative, though she has had multiple sexual encounters, many of them unprotected. Jennie tests positive for HIV. She claims to have had sex only once, with Telly. Jennie spends the rest of the film trying to find Telly, who has taken to only having sex with virgins on the premise that he cannot get STDs this way. Telly and Casper walk to Telly's house and steal money from Telly's mother. They go to Washington Square Park and buy a "dime bag" of marijuana from a Rastafarian. They then meet up with a few friends, one of whom gives a blunt-rolling tutorial, to talk and smoke. Casper rides on a skateboard and carelessly bumps into a man, who furiously threatens him. He pushes Casper over, but is struck in the back of the head with a skateboard by Harold (Harold Hunter), a friend of Telly and Casper's, causing him to collapse. Many of the other skaters join in, kicking and hitting the man until he is unconscious.
Telly and the group from the park pick up a thirteen-year-old girl named Darcy (Yakira Peguero). She is the younger sister of an acquaintance and Telly wants to have sex with her because she is a virgin. He convinces her to go with them to a pool. The other girls engage in pseudo-lesbian kissing and flirtation, but Darcy is restrained, though not shocked by the others' behavior. Telly and the group go to another friend Steven's house to smoke, drink and talk about sex. Meanwhile, Jennie goes to a rave called NASA trying to find Telly, but instead bumps into "Fidget" (Harmony Korine), who gives her "a euphoric blockbuster drug that is supposed to make 'special K' look weak". After taking the drug, which has effects similar to a depressant, she finds out that Telly is at what has become a party at Steven's house.
Jennie arrives at the party to discover Telly engaging in rough intercouse with Darcy despite her complaining that it hurts, exposing her to HIV. Exhausted by her ordeal and with the drugs still affecting her, Jennie passes out on a couch among the other sleeping party-goers. A drunken Casper proceeds to rape Jennie. The film ends with a soliloquy by Telly about how without sex he would have nothing to live for. The last shot of the film is Casper sitting on a couch naked as he says, "Jesus Christ, what happened?"