Delayed nausea and vomiting is a significant problem for the majority of patients receiving cisplatin. We designed a double-blind randomized study comparing the effects of ACTH and placebo on delayed emesis. Sixty-four adult cancer patients entered this trial; all received a chemotherapy regimen containing cisplatin (greater-than-or-equal-to 60 mg/m2) and a combination of metoclopramide and dexamethasone for the control of acute emesis during the period from 0 to 24 h after cisplatin (day 1). Twenty-four hours after cisplatin (day 2) they were randomized to receive 1 mg of ACTH i.m. in its long-acting form, or placebo in an identical vial. All patients were asked to keep a daily record of the incidence and severity of delayed vomiting and nausea for each of the five consecutive 24-h periods after cisplatin administration. Sixty patients were evaluable. The percentages of patients experiencing vomiting in the ACTH and placebo arms were, respectively, 17% vs. 43% on day 2 (24-48 h after cisplatin) (P = 0.04),13% vs. 40% on day 3 (48-72 h) (P = 0.04),20% vs. 34% on day 4 (72-96 h), and 20% vs. 30% on day 5 (96-120 h). During the entire 5-day study period, 33% of the patients in the ACTH group experienced delayed vomiting as opposed to 57% in the placebo arm (P = 0.11). With regard to the severity of delayed vomiting it was observed that the patients treated with ACTH had a significant reduction in the number of emetic episodes on day 2 (P = 0.01) and day 3 (P = 0.03) as well as throughout the entire 5-day study period (P = 0.04). No statistically significant differences were observed between the two arms with regard to the incidence and severity of delayed nausea. No treatment-related side effects were reported. Our results show that 1 mg of ACTH is safe, well-tolerated and reduces the incidence and severity of delayed vomiting, particularly on days 2 and 3 (24-72 h) after cisplatin. On the succeeding days there was a loss of activity, and further studies with repeated doses of ACTH are needed for prolongation of the period of protection.