We studied the effect of the 5-HT₃ receptor antagonist ondansetron (4 mg orally) on some of the psychological effects of a small dose of alcohol (580 ml of 3.6% alcohol content by volume of lager) in 16 healthy male volunteers using a double-blind placebo controlled, Latin Square cross-over design. Pretreatment with ondansetron significantly attenuated several of the subjective pleasurable effects of alcohol, and also decreased the subjective desire to drink. These findings are consistent with preclinical studies suggesting that the reinforcing properties of alcohol may be attenuated by 5-HT₃ receptor blockade.