A randomized trial was performed comparing the antiemetic efficacy of methylprednisolone (MPN) and metoclopramide (MCP) in 60 breast cancer patients eligible for outpatient adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-FU (CMF). At the time of their first chemotherapy course patients were randomized to receive either MPN 375 mg or MCP 1 mg/kg both administered in 3 equal doses, IV just prior to chemotherapy and then IM 6 and 12 hours after treatment. Patients receiving MPN experienced significantly less nausea (p less than 0.0005) and vomiting (p less than 0.0005) and antiemetic protection was maintained in patients receiving multiple chemotherapy courses. Complete protection (0 emesis) was observed in 58% of patients receiving MPN as compared with 20% of patients treated with MCP (p less than 0.005). The most frequent side effects were facial flush in 38% of patients and somnolence in 15% of patients receiving MPN and MCP, respectively. Complete protection from CMF-induced gastrointestinal side effects was observed in two-thirds of our patients receiving antiemetic MPN treatment. In these patients administration of the maximum cumulative CMF dose was possible without impairing their quality of life. MPN, at the dose and schedule reported, is an affective antiemetic drug suitable for use in breast cancer outpatients receiving adjuvant CMF therapy.