We have evaluated the efficacy of ondansetron in the prevention of opioid-induced pruritus in a prospective, randomized, double-blind, placebo-controlled study. Using a 'human model' of opioid-induced pruritus, 80 ASA I-II patients about to undergo routine surgery were given either ondansetron 4 mg i.v. or 0.9% saline i.v. (40 in each group), 30 min before alfentanil 10 mg kg(-1) i.v. During the following 5 min, patients were observed for signs of perinasal scratching and at 5 min were asked about symptoms of pruritus. The study was then terminated and anaesthesia was induced. There was a significant reduction in the incidence of scratching in patients receiving ondansetron compared with placebo (42.5% vs 70%, respectively, P=0.013). The incidence of itching in the ondansetron group was less than that in the placebo group but this was not statistically significant (30% vs 42.5%, respectively, P=0.245). We conclude that the 5-HT3 antagonist ondansetron may have a role in the management of opioid-induced pruritus.