A double-blind trial to evaluate the antiemetic effects of adrenocorticotropic hormone (ACTH) in patients treated with cisplatin was performed. Thirty-seven adults with advanced cancer who were treated with cisplatin were randomly assigned to receive either synthetic long-acting ACTH (1 mg IM given 24 hours, 12 hours, and immediately preceding the administration of cisplatin) or a placebo given under the same conditions. All of the patients received chlorpromazine (50 mg IM) 30 minutes before cisplatin infusion. Patients receiving ACTH and chlorpromazine had significantly fewer episodes of vomiting (p less than 0.01) and shorter periods of nausea (p less than 0.02) than patients receiving placebo and chlorpromazine. Patients receiving ACTH and chlorpromazine were significantly more comfortable than patients receiving placebo and chlorpromazine. No important side effects were observed. ACTH may be an effective agent in preventing nausea and vomiting induced by cisplatin.