This study investigated the antiemetic properties of four different doses of prochlorperazine (10 mg, 20 mg, 30 mg, 40 mg) when given randomly to patients receiving four cycles of the same dose of cisplatin-based chemotherapy. Prochlorperazine was given to 71 patients by slow intravenous infusion 30 minutes before and 3 and 6 hours after the start of cisplatin chemotherapy. The higher doses of prochlorperazine proved to be effective in the control of cisplatin-induced emesis. For the 20 patients who completed all 4 study cycles of treatment, a relationship was discerned between the dose of prochlorperazine administered and the antiemetic effect. When all 71 patients were analyzed in terms of the results of the first cycle of chemotherapy, a significant dose-response effect was also found. Overall toxic reactions in 82 treatment cycles using either 30 mg or 40 mg of prochlorperazine were dystonia (1 patient), restlessness (2), hypotension (3), and drowsiness (12). This study demonstrates that higher-than-conventional doses of prochlorperazine have an impressive antinauseant effect with only moderate toxicity.