Plasma cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and androstenedione (delta4-A) were measured by RIA during ACTH infusion in preadrenarchal children with constitutional short stature, normal adults, and patients with secondary adrenal insufficiency resulting from hypothalamic-pituitary disease or corticosteroid therapy. The plasma levels of all four steroids were decreased in patients with secondary adrenal insufficiency compared to normal adults, but the decrease in DHA and DHAS was considerably greater than that in cortisol and delta4-A, resulting in significant decreases in the plasma ratios of DHA to cortisol, DHAS to cortisol, DHA to delta4-A, and DHAS to delta4-A (P less than 0.00001). The decreased DHA and DHAS responses to ACTH persisted in one glucocorticoid-treated patient after glucocorticoid therapy was terminated and the cortisol response to ACTH had normalized. The data suggest that adrenal atrophy due to hypothalamic-pituitary disease or corticosteroid therapy is associated with a greater impairment in the secretion of the delta5 adrenal androgens DHA and DHAS than in the secretion of cortisol and delta4-A, and that the capacity to secrete cortisol and delta4-A recovers more rapidly than the capacity to secrete the delta5 adrenal androgens when corticosteroid therapy is withdrawn.