Female patients with ovarian cancer are at high risk for emesis. A study evaluating the antiemetic activity and tolerability of ondansetron plus dexamethasone compared to metoclopramide plus dexamethasone plus diphenhydramine in this group of patients has been performed. A group of 63 patients with ovarian cancer undergoing cisplatin treatment were enrolled in the study. Vomiting, nausea and other side-effects were evaluated by the investigators during the first 24 h and recorded by the patients on a diary card on days 2-4. Ondansetron plus dexamethasone showed a higher antiemetic activity during the first 24 h after cisplatin administration in all three cycles of cisplatin treatment, giving over 90% complete protection from vomiting at the first cycle. The efficacy of ondansetron plus dexamethasone decreased at the second cycle, but the percentage of complete protection from vomiting always remained better than 70%; there was poorer protection in the metoclopramide group, and its effect was similar during all three cycles. Ondansetron plus dexamethasone was also found to be more efficacious than the metoclopramide regimen on the second day after cisplatin administration, while on days 3-4 a high rate of complete protection from emesis was achieved by both antiemetic therapies (> 80%). About 40%-55% of patients receiving ondansetron plus dexamethasone and about 65%-85% of patients treated with metoclopramide plus dexamethasone plus diphenhydramine reported nausea or vomiting during days 1-4. Ondansetron plus dexamethasone is more efficacious than metoclopramide plus dexamethasone plus diphenhydramine but new strategies to improve antiemetic efficacy in ovarian cancer patients must be outlined.