Clinical response to high-dose medroxyprogesterone (MPA), administered following three different routes of administration (i.m., p.o. + i.m., p.o.) and monitoring drug plasma levels, was evaluated in pretreated advanced breast cancer patients. Fifty-eight of 68 eligible patients were considered evaluable for response. Age ranged between 36 years and 82 years. Fifty-six of 58 evaluable patients were postmenopausal. An overall remission rate of 48% was achieved with i.m. MPA, 50% with combined (i.m. + p.o.) modalities; only a 19% remission rate was recorded in the p.o. group. Response rate and MPA plasma concentrations were correlated, and a drug level of 80 ng/ml, by means of a GLC method, seems to identify a subset of patients with high probability of response. Only mild toxic effects were recorded.