Fifteen consecutive patients with progressive metastatic prostate cancer who had failed primary endocrine therapy underwent surgical pituitary ablation by transphenoidal hypophysectomy. Eleven patients showed subjective improvement with reduced pain postoperatively. No patient had any evidence of an objective response although duration of survival was longer in subjective responders (15 months) than nonresponders (4 months). Neither the quality nor the duration of the initial endocrine-induced remission predicted the subsequent response to hypophysectomy. The lack of objective improvement in these patients suggests that the subjective responses seen in prostate cancer patients after hypophysectomy may be due to alterations in pain receptive mechanisms rather than to a favorable impact on the disease process itself.