The effect of ondansetron, a 5-HT3 antagonist, in preventing postoperative nausea and vomiting was investigated in a randomized, double-blind, placebo-controlled study of 84 patients undergoing gynecologic operation and receiving the same general anesthetic. The patients received premedication with either 16 mg oral ondansetron, or a matching placebo. The same medication was given postoperatively 8 h after the first dose. During the first hour after recovery from anesthesia, the frequencies of nausea and vomiting were 52% and 40%, respectively, in patients given placebos. In the ondansetron group nausea and vomiting developed in 17% and 12%, respectively, values significantly different from those with placebos (P less than 0.005). Similar differences were observed throughout the entire 24-h period after recovery, the incidence of nausea and vomiting being 67% and 60%, respectively, in the placebo group and 29% and 26% in the ondansetron treatment group. Ondansetron appears to be a promising antiemetic for the prevention of postoperative nausea and vomiting.