This paper describes a multicentre, double-blind, parallel group study which compared ondansetron (0.15 mg/kg i.v. x 3) plus dexamethasone (20 mg i.v.) with metoclopramide (3 mg/kg i.v. x 2) plus dexamethasone (20 mg i.v.) and diphenhydramine (50 mg i.v.) for the prevention of cisplatin-induced emesis and nausea. Two hundred and eighty-nine consecutive patients receiving chemotherapy containing cisplatin at doses > or = 50 mg/m2 entered the study and 267 patients were evaluable for efficacy. The ondansetron regimen was significantly superior compared with the metoclopramide regimen in the control of acute emesis and nausea. Ondansetron plus dexamethasone provided complete protection against retching and vomiting in 79% of patients compared with 59% of patients given the metoclopramide combination (p < 0.002). Similarly ondansetron plus dexamethasone completely prevented nausea in 77% of patients, whereas the metoclopramide combination protected 66% of patients (p < 0.051). Success (no nausea and no emesis) was afforded to 69% of those patients given ondansetron plus dexamethasone as opposed to 50% of patients given the metoclopramide combination (p < 0.003). From day 2-4 all patients received the same anti-emetic regimen of oral metoclopramide and intramuscular dexamethasone. Significantly fewer patients who had received the ondansetron regimen on day 1 vomited on days 2 and 3 compared with those who had received the triple drug combination (84-86 and 68-71%, respectively, p < 0.006). Nausea was also better controlled in this group on day 2. On subsequent cisplatin cycles, the incidence of acute vomiting rose to 53% in those patients given the metoclopramide regimen, but remained low (26%) in the group treated with ondansetron plus dexamethasone. Patients receiving the metoclopramide regimen had significantly more sedation than patients receiving ondansetron plus dexamethasone (12 vs. 2%; p < 0.005). Extrapyramidal reactions were only observed in metoclopramide-treated patients (3%). The results of this study suggest that ondansetron plus dexamethasone is a more effective and better tolerated anti-emetic regimen compared with metoclopramide plus dexamethasone and diphenhydramine for the prevention of acute cisplatin-induced emesis.