GR 38032F (ondansetron) is a selective serotonin subtype-3 receptor antagonist with reported antiemetic efficacy in patients receiving cisplatin. This study evaluated the safety and efficacy of ondansetron in three consecutive nonrandomized groups of patients who were receiving a 4- or 5-day regimen of cisplatin (20 to 40 mg/m2/d) combination chemotherapy. Thirty-six patients were enrolled. Thirty-five patients were assessable for efficacy. All patients received three daily intravenous doses of 0.15 mg/kg of ondansetron. Twenty-four patients had received no prior chemotherapy. Twelve of these received ondansetron every 2 hours and 12 received ondansetron every 6 hours. Twelve additional patients who had received at least one prior course of chemotherapy were administered ondansetron every 6 hours. All patients were monitored for emetic episodes (vomiting or retching), adverse events, and laboratory safety parameters. Ten patients (29%) had no vomiting or retching throughout the entire study period and 18 patients (51%) experienced two or fewer emetic episodes during the entire study period. The greatest antiemetic efficacy was on day 1 when 27 patients (77%) had no emesis. The chemotherapy-naive patients responded better than the nonnaive patients on all study days. Reported adverse events were minor, with the most common possibly drug-related event being headache (14% of patients). No extrapyramidal symptoms were observed. Transient increases in total SGOT, and SGPT were observed in some patients.