We have performed an open parallel randomized study of the efficacy of two antiemetic drug combinations. Dexamethasone (10 mg i.v.), diphenhydramine (25 mg i.v.), and metoclopramide (3 mg/kg, 15 min i.v.) or droperidol (1.25 mg slow push) were given 30 min before and 90 min after start of chemotherapy. Thirty-six patients treated with cisplatin-based regimens (30 mg/m2 × 3 days or 60 mg/m2 day 1 only), have been observed for 48 h after their last chemotherapy. Twelve (67%, confidence interval 95%: 41–87%) experienced no vomiting while on metoclopramide and 11 (61%, confidence interval 36–83%) were protected by droperidol. Further patient accrual was stopped because of side effects in one study arm. Moderate sedation (difficulty to keep up a conversation) was observed in 48% of those on metoclopramide versus 14% of those on droperidol (p < 0.05). We conclude that low-dose droperidol combinations can offer antiemetic protection for patients treated with moderate-dose cisplatin-based chemotherapies. In view of the potential for severe long-term neurologic problems due to metoclopramide or droperidol, these and similar drugs should be used at the lowest possible