The antiemetic efficacy and toxicity of methylprednisolone (MP) and metoclopramide (MTC) in prevention of nausea and vomiting in breast cancer patients receiving intravenous cyclophosphamide methotrexate 5-fluorouracil (CMF) chemotherapy has been evaluated in a double-blind trial. The two antiemetic drugs (MP vs. MTC) offered the majority of patients a similar complete protection from vomiting (76.5 vs. 66.7%) and nausea (82.4 vs. 81.8%), but in older patients MTC seems more efficacious than MP. Sedation was found more frequently (p = 0.02) in patients treated with MTC. In conclusion, in patients treated with CMF the use of MP as preventive therapy of nausea and vomiting is to be preferred to MTC due to its better tolerability, but in older patients MTC should be considered if MP fails.