This study assessed the efficacy and safety of dolasetron compared with ondansetron for the prevention of nausea and vomiting during high-dose myeloablative chemotherapy followed by peripheral blood stem cell support. Twenty centers randomized 197 patients to receive dolasetron 100 mg intravenously (I.V.) followed 8-12 hours later by a single oral dose of dolasetron 100 mg or ondansetron 32 mg I.V., followed 8-12 hours later by a single oral dose of ondansetron 8 mg during high-dose chemotherapy (HDC) regimens for breast cancer (n = 96; 48.7%), non-Hodgkin's lymphoma (n = 83; 42.1%), or Hodgkin's disease (n = 18; 9.1%). All patients received a daily I.V. bolus of dexamethasone 10 mg with study antiemetic agents and a continuous infusion of diphenhydramine, lorazepam, and dexamethasone (ie, BAD pump) throughout the course of the study, with patient-controlled on-demand bolus doses as needed. After completing a daily diary of emetic episodes and rescue medication use, 164 of 197 patients were evaluable. Total plus complete responses (no emesis, no nausea, no rescue) over the entire study period were achieved in 45.7% and 46.9% of patients on the dolasetron and ondansetron arms, respectively. Dolasetron and ondansetron were well-tolerated. This study demonstrates that dolasetron and ondansetron are equally safe and effective in the prevention of nausea and vomiting associated with HDC (P = 0.955).