BACKGROUND: To compare the efficacy and safety of ondansetron(OND) vs tropisetron (TRO) vs chlorpromazine (CHL) + dexamethasone (DEX) in children receiving highly and moderately emetogenic chemotherapy .PATIENTS AND METHODS: Children with solid malignant tumors who were chemotherapy-naive, were randomized in a double-blind, placebo, cross-over trial in order to be administered CHL 0.3 mg/kg and DEX 2 mg/m2 intravenously (i.v.) 30 min before and 12h after chemotherapy or TRO 0.2 mg/kg i.v. 30 min before and 12h after chemotherapy as antiemetic therapy .RESULTS: 46 patients for a total of 302 chemotherapy cycles were evaluated. Highly emetogenic chemotherapy: A complete response (0 emetic episodes) for emetic episodes was achieved in 34% and 28.1% of the patients in OND and TRO groups respectively, versus 16.7% in CHL + DEX group(p < 0.01). A major response (1-2 emetic episodes/day) for emetic episodes was achieved in 38.3% and 31.2% of the patients in OND and TRO groups respectively, versus 14.6% in CHL + DEX group (p < 0.01). There was no statistically significant differences between OND and TRO groups .Moderately emetogenic chemotherapy: Results did not show any significant differences between the three antiemetics regimens. Adverse events: Somnolence was more frequent in patients submitted to CHL + DEX regimen (57.8%) than in OND (16.5%) and TRO (7.5%) groups (p < 0.001).CONCLUSIONS: OND and TRO regimens were superior to CHL + DEX in children receiving highly emetogenic chemotherapy. Efficacy of the three antiemetics regimen was similar in moderately emetogenic chemotherapy.