The discovery of specific behavioral effects of several neuropeptides and the expanded appreciation of a wide range of endocrine disturbances in depressive illness have recently renewed interest in the nature of the relationship between mood and endocrine changes. Major depressive disorders are a major and life-threatening complication of Cushing's syndrome, Addison's disease, hyperthyroidism, hypothyroidism and hyperprolactinemic amenorrhea. A treatment primarily directed to the physical condition may be more effective than antidepressant drugs in such organic affective syndromes. The influence of hormonal disturbances in the development of depression in Conn's disease, pheochromocytoma, parathyroid disturbances, SIADH, acromegaly, hirsutism and other endocrine diseases should be individually evaluated. Antidepressant drugs remain the most specific and readily available treatment of major depressive disorders in the setting of endocrine illness.