Sixty five chemotherapy naive patients receiving cisplatin (50-120 mg/m2) containing chemotherapy participated in an evaluation of ondansetron, a 5-HT3 receptor antagonist, in the prophylaxis of acute and delayed nausea and emesis. Ondansetron was given as three 0.15 mg/kg doses intravenously (0.5 h before, 3.5 h and 7.5 h after cisplatin) for acute emesis followed by 8 mg orally 8-hourly for five days at 24 h post-cisplatin for delayed emesis. For acute emesis (first 24 h, n = 63), complete control was achieved in 34 patients (54%) and major control (1-2 episodes) in 16 patients (25%). Complete protection from acute nausea was achieved in 48 patients (76%). For delayed emesis (days 2-6, n = 55), 33 patients (60%) were completely protected or reported one to two episodes during the entire 5-day observation period; 63% reported only mild or no nausea. Ondansetron was well tolerated with no significant drug-related adverse events. These results are consistent with serotonin being a significant transmitter of cisplatin-induced emesis.