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Ronna (Sarah Polley), working overtime to avoid being evicted, is approached at work by Adam (Scott Wolf) and Zack (Jay Mohr), asking if she can supply 20 hits of ecstasy, which they were hoping to buy from her co-worker Simon (Desmond Askew). Realizing she can profit from the deal, she approaches Simon's dealer Todd Gaines (Timothy Olyphant) for the drugs, but as she is unable to pay, leaves her friend and co-worker Claire (Katie Holmes) with Todd while she makes her deal.
On trying to make the deal, Ronna grows suspicious of Burke (William Fichtner), a stranger with Adam and Zack, who presses her for the drugs. In a panic she flushes the drugs down the toilet and leaves. Ronna then steals aspirin to replace the ecstasy she disposed of, helped by her friend and co-worker Mannie (Nathan Bexton), who had swallowed two of the pills without knowing their strength.
Ronna returns the pills to Todd and she, Claire and Mannie make their way to a rave. Todd soon discovers the pills are fake and pursues Ronna, discovering her at the rave. Ronna flees with Mannie but he is overcome by the drugs. Ronna leaves him in an alley and promises to return with her car, but Todd confronts her with a gun in the parking lot. Before he can shoot Ronna, she is hit by a car which speeds away.
The story restarts from the perspective of Simon, who is going to Las Vegas with his three friends Marcus (Taye Diggs), Tiny (Breckin Meyer), and Singh (James Duval). Singh and Tiny get food poisoning, leaving Simon and Marcus to their own devices. Simon crashes a wedding and has sex with two of the bridesmaids before their hotel room accidentally catches fire. Marcus and Simon leave the hotel, stealing a car from someone who thinks Marcus is a parking attendant.
The pair go to a strip club where Simon orders a lap dance using Todd's credit card for security, but enrages the bouncer Victor Jr. by groping one of the strippers. Simon shoots Victor Jr. with a gun he found in the stolen car, and he and Marcus flee to the hotel, rousing Tiny and Singh. The four barely escape the bouncer and his father, Victor Sr. (J. E. Freeman), but Victor Sr. traces Todd's address from the credit card Simon left at the strip club.
The story then changes perspective to Adam and Zack, actors in a daytime soap opera, who are secretly gay and in a relationship. Having been caught in a drug deal they are forced to work with Burke, a police detective, to entrap their dealer. Adam is fitted with a wire. When they cannot find their usual dealer Simon at the store where he works, the two convince Ronna to come up with the drugs. When Ronna arrives later to make the deal, Zack secretly warns her away and she disposes of the drugs in the bathroom.
After the unsuccessful bust, Burke invites Adam and Zack to Christmas dinner. Adam and Zack observe strange behavior from Burke and his wife Irene (Jane Krakowski), Burke espousing the quality of his bed to Zack while naked, and Irene coming onto Adam. Burke finally pitches an Amway-type company to Adam and Zack over dinner, but the pair make excuses and leave.
Idly discussing their infidelity to each other, Adam and Zack realize they both had cheated with the same person, Jimmy. They discover he is at a rave and confront him there, cutting his long hair. While leaving the rave they accidentally run over Ronna in the parking lot, panicking and driving away when they see Todd's gun.
Zack tries to reassure Adam that even if Ronna had survived being run over, Todd would have shot her. Adam then discovers to his horror that he is still wearing his wire. Fearing they have been recorded and will be discovered, the two return to the accident scene to remove Ronna's body, but discover she is still alive. They prop her up on a car, setting off its alarm, and watch from a distance as other party-goers call for an ambulance.
Claire goes to a restaurant where she hoped to meet up with Mannie and Ronna, and sees Todd instead. Claire starts talking to Todd and the two soon go back to Todd's apartment building. While making out on the stairs, they are confronted by Victor Jr. and Sr. Todd offers Simon's address just as Simon arrives, having hoped to hide for a few days. There is a scuffle but it is stopped by Claire, who refuses to witness a murder. As a form of 'justice', Simon agrees to be shot in the arm by Victor Jr. Claire leaves in disgust, and hears a gunshot.
Ronna wakes up, to her confusion, in a hospital, and hobbles back to the supermarket, where Claire is also working. Realizing she left Mannie at the rave, Ronna and Claire return to the venue to find Mannie pale and shaken in an alley. The three go to Ronna's car, where Ronna muses that she can pay her rent. Mannie asks, to the incredulity of Ronna and Claire, what their plans are for New Year's.

Question: who refuses to witness a murder?
Answer: scuffle