Among a consecutive unselected series of 29 patients with Cushing's syndrome 21 had bilateral adrenal hyperplasia and 8 had tumours. Twenty-five (86 per cent) were significantly depressed; three of the tumour patients, but only one of the hyperplasia group were free of symptoms so that if there are no psychiatric symptoms there is a three in four chance that the patient has a tumour. There was a family history of depression or suicide or a history of early bereavement or separation in half the cases. In six of the hyperplasia patients a major emotional disturbance had preceded the onset, and in five this was a loss. The severity of the depression was not related to the level of circulating cortisol. The depression was rapidly relieved when the tumour or hyperplastic glands were removed. Depression in Cushing's syndrome might result from a substance other than cortisol produced by the adrenal under excessive pituitary and/or hypothalamic stimulation, which could play a part in the aetiology of depressive illness in general.