This prospective, randomized, double-blind, placebo-controlled study evaluated the antiemetic efficacy of preoperative oral ondansetron, 0.075 mg/kg or 0.15 mg/kg, in 136 preadolescent children premedicated with midazolam 0.5 mg/kg per os and dexamethasone 0.1 mg/kg intravenously prior to undergoing tonsillectomy with isoflurane anesthesia. The incidence of vomiting during the 24 h after tonsillectomy was significantly reduced (P < 0.04) by ondansetron 0.15 mg/kg compared with placebo and ondansetron 0.075 mg/kg (15%, 38%, and 36%, respectively). There was a significant reduction (P < 0.03) in the mean number of vomiting episodes per patient during the 24 h immediately after tonsillectomy in the ondansetron 0.15 mg/kg group compared with the placebo and ondansetron 0.075 mg/kg study groups (0.2 +/- 0.6, 0.8 +/- 1.3, and 0.8 +/- 1.3, respectively). The need for antiemetic rescue therapy (ondansetron 0.15 mg/kg intravenously after three episodes of emesis prior to discharge) was significantly greater in children who received placebo compared with the ondansetron 0.15 mg/kg study group (13% vs 0%, P < 0.05). We conclude that ondansetron 0.15 mg/kg, administered orally prior to tonsillectomy, is associated with reduced postoperative vomiting in preadolescent children. In addition, the preoperative oral administration of ondansetron 0.075 mg/kg is no more effective than placebo in preventing posttonsillectomy vomiting in preadolescent children.