RU486 is a synthetic glucocorticoid antagonist. The authors used RU486 to examine the hypothesis that the elevated plasma cortisol and ACTH in patients is due to suprahypophyseal stimulation of the anterior pituitary. Seven patients and matched controls were studied before and after the administration of RU486. RU486 produced an increase in HPA activity in depressed patients. Thus providing support for the hypothesis that there is increased suprahypophyseal stimulation of the anterior pituitary.