The aim of this study was to evaluate the efficacy and safety of ondansetron, an antagonist of 5-hydroxytryptamine type 3 (serotonin 3) (5-HT3) receptors, in controlling nausea and vomiting induced by antineoplastic therapy in children affected by cancer. Six patients affected by nausea and vomiting due to antineoplastic drugs were treated with ondansetron (4 mg/m2). Urinary samples for the assay of serotonin and 5-hydroxy-indoleacetic acid (5-HIAA) were collected 24 hr before antineoplastic drug treatment, 24 hours after the start of antineoplastic therapy and, 24 hr after the start of ondansetron therapy. All patients were affected by nausea and vomiting within two to four hr after the antineoplastic treatment. Urinary concentrations of serotonin and 5-HIAA were higher and statistically significant (P < 0.01) with respect to basal values. Treatment with ondansetron significantly reduced the number of episodes of nausea and vomiting, as well as the urinary values for serotonin and 5-HIAA.