This study compared high-dose metoclopramide and prochlorperazine for their antiemetic activities in the treatment of patients with solid tumors receiving cisplatin-based cancer chemotherapy, in a prospective, double-blind fashion. Sixty patients were entered in the study, and 28 patients on each regimen were evaluable. For regimen 1, metoclopramide was given intravenously (IV) over 15 minutes at a dose of 2 mg/kg 30 minutes before, 30 minutes after, and three hours after treatment with cisplatin. In regimen 2, prochlorperazine was given IV 30 minutes before and three hours after the cisplatin; a placebo was administered at 30 minutes after cisplatin. There was no statistically significant difference between the two regimens in their antiemetic efficacies during the first three hours. For emesis that occurred from three to 24 hours after administration of cisplatin, prochlorperazine was marginally superior. The median number of emeses in the metoclopramide regimen was 2.5 (range, 0 to 10+) compared to 1.0 (range, 0 to 10+) in the prochlorperazine regimen. This is not a significant difference. The overall incidence of adverse reactions was greater in the metoclopramide regimen, with drowsiness being the most common toxicity for both antiemetic programs. Thus, IV high-dose metoclopramide and prochlorperazine are similar and effective in the management of cisplatin-induced emesis. IV prochlorperazine at 20-mg dosage is surprisingly effective.