Available clinical data on the use of oral ondansetron for the prevention of nausea and vomiting in patients undergoing cancer chemotherapy or surgery are reviewed. Injectable ondansetron hydrochloride is very effective in preventing nausea and vomiting associated with even the most emetogenic antineoplastic drugs. In December 1992, 4- and 8-mg oral tablets (ondansetron hydrochloride dihydrate) became available. Many of the clinical trials of oral ondansetron have not compared it with other antiemetics or have compared it only with placebo. Oral ondansetron has shown efficacy in such trials, but the standard of care for preventing chemotherapy-induced emesis is not placebo. Studies involving a prechemotherapy i.v. dose of ondansetron followed by oral therapy have shown high response rates for the whole study period; however, when day 1 is excluded, the results are not impressive for the remainder of the study period. It seems that the period beyond 24 hours is when oral ondansetron is effective, and that efficacy against acute emesis is due to i.v. ondansetron. Clinical trials in which oral ondansetron and oral metoclopramide were compared showed ondansetron to be, at best, equal to metoclopramide. One study showed the combination of dexamethasone and metoclopramide to be superior to oral ondansetron. Oral ondansetron is more effective than placebo in preventing post-operative nausea and vomiting in gynecologic surgery patients; however, there have been no comparative studies, and routine use of antiemetics in most surgical patients may be unnecessary because newer anesthetics are less emetogenic. Although the adverse effects of oral ondansetron are milder than those of standard antiemetics, this may not compensate for the drug's high cost. Oral ondansetron is not superior to traditional antiemetics for the prevention of nausea and vomiting caused by chemotherapy or surgery.