Hypophysectomy was performed in six patients with advanced carcinoma other than from breast and prostate gland to alleviate pain. Two patients received significant and lasting relief of pain; one achieved relief but died from progression of disease 5 weeks after surgery; one patient, initially relieved, had recurrence of pain 3 months later; one had about 50% relief; and one received no benefit. Possible mechanisms for pain relief include changes in pituitary hormones, prostaglandins, and the newly isolated brain peptides, alpha and beta endorphin. These preliminary observations will require further critical evaluation in a larger series to determine the effectiveness of hypophysectomy in relieving pain in cancer other than from the breast and prostate. The results, nevertheless, do imply that a different approach to pain, namely endocrine manipulation, may be beneficial in certain cancer patients.