A phase II trial of sequential oral medroxyprogesterone acetate (MPA) and epirubicin was performed in 12 postmenopausal women with advanced breast cancer. Patients received MPA at a dose of 500 mg twice daily by mouth for 25 days. Following a 3-day washout, epirubicin was administered in a dose of 75 mg/m2. After a 3-week hiatus, the cycle was recommenced with MPA. Responses were evaluated at the end of the first 25-day period of MPA and following the end of the first cycle. Partial responses were obtained in two patients (17%)--one after the first 25 days of MPA and the other at the end of the first cycle. One of the patients had chest wall disease and the other had hepatic involvement with ascites. Minimal toxicity was experienced from this regimen and the response durations were 2 and 7 months. The response rate reported here does not warrant the further development of sequential therapy. The dose intensity of both MPA and epirubicin are compromised and may be the cause of this low response rate.