In this randomized study, the efficacy of a single dose of three serotonin antagonists were compared in prophylaxis of acute and delayed vomiting induced by moderately emetogenic, single-day chemotherapy in chemotherapy-naïve patients. A total of 54 patients were entered. Eighteen patients received ondansetron, 17 received tropisetron, and 19 received granisetron. Antiemetics were administered as 15-minute intravenous infusion before chemotherapy. Complete control of acute vomiting was achieved in 38.8% with ondansetron, 58.8% with tropisetron, and 73.7% with granisetron. Major response rates were 83.3%, 82.3%, and 89.5%, respectively. For the delayed control of emesis, complete control of delayed vomiting was achieved in 38.8% with ondansetron, 52.9% with tropisetron, and 73.7% with granisetron. The major response rates were 71.8%, 70.5%, and 100%, respectively. The adverse effects were rare and mild in all groups. The authors conclude that there may be clinically important differences among serotonin antagonists used for chemotherapy-induced emesis.