In a retrospective review the response of 67 patient with metastatic adenocarcinoma of the prostate to the administration of exogenous testosterone was analyzed. Among 52 patients in whom objective and/or subjective responses were evaluable 45 experienced unfavorable responses. There was prompt regression of most unfavorable responses with testosterone withdrawal. The duration of treatment required to evoke an unfavorable response was related to the clinical status of the patient. Twenty-five per cent of patients with symptomatic metastases who had received no prior treatment, 36 per cent in symptomatic remission after endocrine therapy and 94 per cent with symptomatic relapse after endocrine therapy experienced unfavorable responses within 30 days of treatment. No patient had objective evidence of tumor regression during testosterone therapy but 7 patients, 6 with remission and 1 untreated, experienced symptomatic benefit. We conclude that the response of patients with metastatic prostate cancer to exogenous testosterone is related to the mass and endocrine treatment status, and that exogenous testosterone can stimulate prostatic neoplasms that proliferate in the absence of normal endogenous testosterone levels.