During the human aging process, basal plasma levels of cortisol and aldosterone demonstrate little change, while concentrations of adrenal androgens (AA) such as dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and androstenedione (A) decrease dramatically in men and women. There is no age-related change in ACTH concentrations to explain this observation. In this study, ACTH (cosyntropin, alpha1-24 corticotropin) stimulation tests were performed on elderly subjects and controls to test the hypothesis that analogous to the aging testicular. Leydig cell, AA-producing cells of the aging adrenal gland may become less sensitive to physiological levels of ACTH, but still retain their sensitivity to elevated ACTH levels. Results showed that in the elderly subjects, basal levels and ACTH-stimulatability of cortisol and aldosterone were unchanged. In agreement with earlier studies, basal levels of AA were found to be decreased in the elderly. However, ACTH stimulation demonstrated impaired reserve in DHA and A, and a total lack of stimulatability of DHAS. These findings could be explained by an age-related loss of adrenal enzymes or cell populations which produce AA, a loss or decrease in a subpopulation of ACTH receptors specific for AA production, or loss of a pituitary factor necessary for AA secretion.