PURPOSE: This pilot, open-label study evaluates the antiemetic efficacy and safety of a single 20-mg intravenous (IV) dose of dexamethasone combined with a single IV dose of ondansetron (32, 24, or 8 mg) in patients receiving highly emetogenic (HE), moderately high emetogenic (MHE), or moderately emetogenic (ME) chemotherapy, respectively. PATIENTS AND METHODS: One hundred forty-six patients received a single 20-mg IV dose of dexamethasone over 15 minutes beginning 45 minutes before chemotherapy and either a single 32-, 24-, or 8-mg IV dose of ondansetron over 15 minutes beginning 30 minutes before chemotherapy. Patients were evaluated for emetic episodes, extent of nausea, and adverse events for 24 hours after chemotherapy. RESULTS: Complete response (no emetic episodes) was noted in 72% (95% confidence interval [CI], 60% to 84%), 88% (95% CI, 79% to 97%), and 77% (95% CI, 63% to 92%) of patients in the HE, MHE, and ME categories, respectively. The proportion of patients who experienced no nausea on the posttreatment assessment was 51% (95% CI, 37% to 64%), 69% (95% CI, 56% to 81%), and 47% (95% CI, 29% to 65%), respectively. The antiemetic regimens were all well tolerated. The proportion of patients with any drug-related adverse events did not vary across the three study groups despite the range of ondansetron doses and variety of chemotherapy regimens. Mild headache was noted in 28% of patients. Other adverse events, all of which were noted in fewer than 10% of patients, included lightheadedness, fatigue, dizziness, and constipation. CONCLUSION: A single IV dose of either 8, 24, or 32 mg of ondansetron combined with a single 20-mg IV dose of dexamethasone resulted in good control of acute emesis across a wide spectrum of chemotherapy regimens. Nausea control proved somewhat more difficult, with approximately 50% of patients in the HE and ME emetogenic categories experiencing some degree of nausea. The results of our pilot study suggest that adjusting the dose of ondansetron to the intrinsic emetogenicity of the chemotherapy regimen permits a more efficient use of ondansetron while maintaining good antiemetic control. Such an approach appears worthy of further investigation.