This was a multicentre, randomised, double-blind, parallel-group study which included female breast cancer patients, receiving their first of 6 scheduled courses of chemotherapy (cyclophosphamide greater than or equal to 500 mg/m2). Patients received an intravenous dose of 16 mg dexamethasone with either 8 mg ondansetron or 60 mg metoclopramide before chemotherapy, followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. A total of 93 patients were treated with ondansetron and 94 patients with metoclopramide. On day 1 of their first course of treatment 91 and 60% of patients in the ondansetron and metoclopramide groups respectively were free of emesis (p less than 0.001). Over the 5-day treatment period, the corresponding figures were 81 and 48% (p less than 0.001). The results for nausea also revealed highly statistically significant treatment differences (p less than 0.001) in favour of ondansetron for both day 1 and day 1-5 analyses of the first treatment course. Over the series of courses, 67% of patients receiving ondansetron completed all 6 courses with a maximum of 2 emetic episodes on their worst day, compared with 28% of patients receiving metoclopramide (p less than 0.001). A similar analysis for nausea revealed that 49% of patients receiving ondansetron completed all 6 courses with 'none' or 'mild' nausea compared with 27% of patients receiving metoclopramide (p less than 0.001). These differences were reflected in quality of life data (Rotterdam Symptom Checklist). After the first course of treatment, a statistically significant improvement (p = 0.002) in the psychological subscale scores was observed after ondansetron compared with metoclopramide. No differences were observed in the physical or functional activity subscales after the first course. However, the quality of life results over the series of courses revealed a more pronounced difference in favour of ondansetron in the psychological subscale scores (p less than 0.001) as well as trends in favour of ondansetron in the physical (p = 0.096) and functional activity (p = 0.056) subscales. Extrapyramidal symptoms were reported in 19% of patients in the metoclopramide group and resulted in 15% of patients withdrawing from their randomised anti-emetic schedule, either during or between treatment courses. Other adverse events were generally minor in nature and did not necessitate withdrawal from treatment. In conclusion, this study shows that ondansetron is significantly superior to metoclopramide (each with a single pre-treatment dose of dexamethasone) in the control of emesis over 6 courses of chemotherapy for breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)