Children undergoing neurosurgical resection are at high risk for postoperative nausea and vomiting. Ondansetron, a selective serotonergic (5-HT3) antagonist, is effective in reducing postoperative vomiting in several high-risk populations. In a prospective, randomized study, we compared the prophylactic use of intravenous ondansetron, 0.15 mg/kg, versus placebo for the prevention of emesis in 60 children, aged 2-18 yr, undergoing craniotomies for resective procedures. Patients with preoperative emesis were excluded from the study. All patients were tracheally extubated at the conclusion of surgery, and each episode of emesis during the first 24 postoperative hours was recorded. For the entire 24-h interval, the incidence of emesis in children who received ondansetron (57%) was not significantly different from that in those who received placebo (66%); however, in the first 8 h, the incidence was 25% (ondansetron) vs 44% (placebo) (P = not significant). In those receiving placebo, there was no difference in emesis between patients undergoing operations above versus below the tentorium. Although our sample size was too small to completely exclude any beneficial effect, ondansetron appears ineffective in preventing postoperative emesis in this patient population.