Thirty patients with hormone-resistant metastatic progressive prostatic carcinoma were treated with sequentially alternating hormone chemotherapy. They were given 1,000 mg medroxyprogesterone acetate (MPA) orally for 26 days followed by intravenous doses of 25 mg/m2 epirubicin weekly for 4 weeks. The median duration of the treatment was 29 weeks (range 8-84). In 2 patients a more than 50% reduction in the size of measurable lymph node metastases was observed and in 2 others skeletal metastases decreased. Serum acid phosphatase normalized in 6 patients. Twenty-five patients achieved a subjective response (median duration 24 weeks; range 4-76 weeks). Median survival from the start of treatment (30 +/- 16 weeks) was unrelated to the achievement of subjective response. Normalization of serum acid phosphatase and a more than 50% reduction in serum alkaline phosphatase correlated with the achievement of a subjective response. Toxicity was generally mild, but in 1 case therapy was discontinued because of suspected cardiotoxicity. Sequentially alternating high-dose MPA low-dose epirubicin hormone chemotherapy has a marginal objective effect but a good subjective effect on progressing hormone-resistant prostatic cancer.