One hundred eleven patients with endocrine-refractory Stage D prostate cancer were treated with weekly administration of 20 mg/m2 body surface area of doxorubicin hydrochloride (Adriamycin). Fifty-seven were part of a randomized study comparing doxorubicin and prednisone to prednisone alone. There were significantly more subjective responders in the doxorubicin group than in the prednisone group (p < 0.01). The number of patients with evidence of stable disease was also higher during the chemotherapy arm compared with prednisone alone (p = 0.02). Patients taking doxorubicin had a slightly longer period of stable disease than did those taking prednisone (p = 0.08). Overall survival, however, was not prolonged (p = 0.26). Fifty-four patients took part in an open trial and 69 percent responded to treatment. All of these had clinical improvement. Side effects were minimal with cardiotoxicity noted in less than 15 percent among patients with side effects. Over 35 percent had no side effects. Thus single agent, weekly doxorubicin therapy as evaluated in our experience, while well tolerated and of subjective benefit, does not provide the patient with a significant longer progression free survival or improved overall survival.