OBJECTIVE Nausea and vomiting remain the most distressing side effects of cancer chemotherapy. The present study aimed to study the efficacy and tolerability of ondansetron versus (vs) metoclopramide in different dose related grades of cisplatin induced acute emesis. METHODS A total of 137 patients were enrolled and 80 completed the study. Cisplatin 60 mg/m2 was given intravenously (iv) either as a single dose on day 1 (high dose regimen) or in three doses of 20 mg/m2 each on days 1-3 (low dose regimen) along with bleomycin +5-flurouracil in 40 patients each. Patients were randomized in each cisplatin regimen to receive either 20 mg metoclopramide (20 patients) or 8 mg ondansetron (20 patients) iv 30 min prior to cisplatin administration followed by 20 mg metoclopramide or 8 mg ondansetron orally 8 h respectively for 24 h after the last cisplatin administration. Ten patients receiving high dose cisplatin in each group were also given dexamethasone 8 mg iv with the primary antiemetic. Patients were assessed for 24 h after the last cisplatin injection. RESULTS In low dose cisplatin regimen, complete suppression of acute emesis occurred in 65 per cent patients receiving ondansetron versus 30 per cent receiving metoclopramide, while in high dose regimen, complete response rate was 20 per cent with ondansetron versus 0 per cent with metoclopramide. Dexamethasone significantly augmented the antiemetic efficacy of metoclopramide but not that of ondansetron. Protection from nausea in the acute phase was seen in 95 per cent patients receiving ondansetron vs 70 per cent receiving metoclopramide in low dose regimen. With high dose the protection rates were 90 vs 0 per cent respectively. Combination of dexamethasone + metoclopramide achieved 70 per cent protection while dexamethasone + ondansetron was effective in 90 per cent. Dropouts and withdrawals were more among patients receiving high dose cisplatin and antiemetic regimens without dexamethasone. Thirty nine adverse events were reported by 20 out of 80 patients. All adverse events were mild. CONCLUSIONS The results demonstrate dose related emetogenicity of cisplatin and superior antiemetic efficacy of ondansetron, especially against high dose cisplatin regimen. Dexamethasone potentiated efficacy of metoclopramide but not that of ondansetron. The combination of metoclopramide plus dexamethasone was found to be as efficacious as ondansetron monotherapy.