Aims and background Ondansetron, a selective serotonin type 3 receptor antagonist, has been investigated at a wide range of doses. Recent studies have demonstrated that a single dose of this drug is active, either by intravenous bolus or continuous infusion. The main aim of this study was to evaluate the efficacy of a low dose of ondansetron in a simple and feasible schedule as follows: ondansetron 8 mg i.v. and dexamethasone 8 mg i.v. given before chemotherapy on day 1. Oral ondansetron 8 mg was subsequently given in the evening of day 1, and then even 12 hours on days 2, 3 and 4. Methods Forty-chemotherapy-naive patients receiving cisplatin, dacarbazine or other emetogenic drugs were enrolled in the study. All courses of chemotherapy were given in an outpatient setting. Results During the first cycle, complete control of acute emesis was achieved in 88% of cases, and no delayed emesis was recorded in 76%; acute and delayed nausea were absent in respectively 78% and 69% of cases. During the second, third and fourth cycles complete control of acute emesis was achieved in respectively 92%, 80% and 86% of cases, and no delayed emesis was recorded in 71%, 82% and 82%. No severe adverse effects were observed. Conclusions Our study shows that a single intravenous administration of low-dose ondansetron combined with intravenous dexamethasone and followed by oral ondansetron twice daily is effective in controlling emesis in patients receiving chemotherapy, and that it is feasible as an ambulatory regimen.