Cisplatin may evoke both an acute emetic response during the first 24 hours following treatment and a less well-recognized syndrome of delayed emesis. While delayed emesis is usually less severe in terms of frequency of vomiting episodes, the problem continues to result in significant morbidity. In comparison with acute emesis, the exact pathogenesis of the delayed emesis syndrome remains unclear. Although a combination of oral metoclopramide and dexamethasone is effective in many patients in preventing delayed emesis, almost 50% continue to experience at least one emetic episode when treated with this regimen. A phase III multicenter study has evaluated oral ondansetron versus placebo in the prevention of the delayed-emesis syndrome in 50 patients during days 2 through 5 following high-dose cisplatin administration. Although the daily rates of complete emetic control, failure, and control of nausea favor ondansetron, this trial is statistically inconclusive in establishing efficacy of ondansetron as a single agent in the prevention of delayed emesis. Ondansetron was well tolerated in the dose and schedule used.