Lower hemibody radiotherapy is an effective palliative treatment for patients with widespread bone metastases, but is frequently associated with the unpleasant side effects of nausea and vomiting. Patients often require admission to hospital for at least an overnight stay, with its inevitable costs. This study has investigated the clinical efficacy and safety profile of ondansetron, a 5HT3 receptor antagonist, and compared it to a standard antiemetic combination, chlorpromazine and dexamethasone. Sixty-six patients were randomised to receive antiemetic prophylaxis with either oral ondansetron or a combination of chlorpromazine and dexamethasone (33 patients in each arm): 60 were treated with lower abdominal radiotherapy (8 Gy mid- plane dose) and 6 with radiotherapy to the upper lumbar spine (12.5 Gy incident dose). Patients were assessed for severity of nausea and vomiting and for whether they would use the same antiemetic again. Quality of life was assessed using the Functional Living Index Cancer (FLIC) and Functional Living Index Emesis (FLIE) quality-of-life questionnaires. A detailed cost- benefit analysis was also performed. Ondansetron scored highly as an antiemetic, being significantly better at controlling emesis on all four study days (P<0.001) and significantly better at controlling nausea on day 1 (P<0.001) than the standard combination of chlorpromazine and dexamethasone. Quality of life was better in the ondansetron-treated group, and ondansetron was found to be safe with no significant adverse effects. As a result, 98% of patients and investigators would use ondansetron again. Cost-benefit analysis revealed that, when complete control of emesis is the aim, ondansetron is not unduly expensive compared to the standard antiemetic regimen. As ondansetron was clearly effective in patients receiving hemibody irradiation it seems it would be prudent to adopt it for use in such patients routinely. The use of ondansetron would allow them to be treated as outpatients, with the attendant financial and psychosocial benefits of such an approach.