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Melancholia is thought by many investigators to have a biological basis, and biological research, particularly on abnormalities of the neuroendocrine system and of the sleep electroencephalogram, is now beginning to yield results which can help in the differential diagnosis of depressive illness. This review will focus on the most widely studied neuroendocrine disturbance: disinhibition of the hypothalamus-pituitary-adrenal cortex (HPA) system as revealed by the dexamethasone suppression test (DST).