Ondansetron, a selective 5-HT3 antagonist, is known to be effective for preventing emesis induced by cisplatin and other antineoplastic agents. We undertook a randomized double-blind study in a series of bone marrow transplantation (BMT) recipients to assess the antiemetic efficacy and the safety of ondansetron in comparison with chlorpromazine, which was being used at our institution, as the standard antiemetic agent for the conditioning regimen. Forty patients submitted to BMT (21 autologous, 19 allogeneic) were included in the study. Patients were randomly assigned to receive ondansetron (as a loading dose of 8 mg iv one hour before the beginning of the conditioning regimen followed by a continuous infusion of 1 mg per hour for the whole treatment period) or chlorpromazine 60 mg/m2/day given by continuous infusion for the same period (maximum 8 days). Twenty patients were assigned to ondansetron, while 20 were assigned to chlorpromazine. The response rate in terms of antiemetic efficacy and in nausea control was similar between the two treatment groups. On the contrary the two groups differed significantly in regard to side-effects: patients receiving ondansetron experienced significantly less sedation (p = 0.002), the absence of extrapyramidal reactions (p < 0.001) and no need for dose reduction (p < 0.001) as compared with patients treated with chlorpromazine.