Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group, multicenter study. Patients were randomized to receive either 1) dronabinol 10 mg every 6 hr plus placebo; 2) placebo plus prochlorperazine 10 mg every 6 hr; or 3) dronabinol and prochlorperazine, each 10 mg every 6 hr. Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy; all was given orally. Only 29% of patients in group 3 versus 47% in group 1 and 60% in group 2 experienced nausea after chemotherapy. In addition, the median duration per episode and severity of nausea were significantly less with combination therapy. Vomiting occurred after chemotherapy in 41%, 55%, and 35% of patients in groups 1, 2, and 3, respectively. The median duration per episode of vomiting was 1 min in group 3 versus two in group 1 and four in group 2. Side effects, primarily CNS, were more common in group 1 than in group 2; addition of prochlorperazine to dronabinol appeared to decrease the frequency of dysphoric effects seen with the latter agent. The combination was significantly more effective than was either single agent in controlling chemotherapy-induced nausea and vomiting.