Ondansetron is a 5-hydroxytryptamine 3-receptor antagonist which has shown activity in the prevention of cytotoxic-induced emesis. Preliminary non-randomized studies also indicated efficacy in preventing sickness following radiotherapy. The present study was therefore undertaken to compare the efficacy and safety of ondansetron (8 mg tds orally) and metoclopramide (10 mg tds orally) in preventing sickness after single-exposure radiotherapy treatments of 8-10 Gy to the upper abdomen. Of 82 evaluable patients 38 received ondansetron and 44 metoclopramide. On the first day after irradiation vomiting or retching was prevented in all but one of the patients on ondansetron whereas metoclopramide achieved complete control of these symptoms in only 46% of subjects (P less than 0.001). Similarly nausea was significantly better controlled by ondansetron in the first 24 hours after treatment (P = 0.001). Complete or major control of vomiting or retching was maintained for 92%-100% of patients on ondansetron during the five days of the study period. In the metoclopramide group the proportion of patients with equivalent control improved from 70% on day 1 to 95 on day 5. Both drugs were well-tolerated.