To elucidate the controversial point whether, in analogy with delta 5-steroid secretion, adrenal delta 4-steroid secretion is significantly decreased in elderly persons, we studied the response of plasma levels of both delta 5-steroids (dehydroepiandrosterone, 17-hydroxypregnenolone, and pregnenolone) and delta 4-steroids (cortisol, androstenedione, 17-hydroxyprogesterone, and progesterone) to acute ACTH stimulation in four groups of young and elderly males and females, respectively. To study the possible influence of sex hormones on adrenocortical function in elderly persons, we performed the same study in male with prostatic carcinoma treated with estrogens. The data show that in elderly persons, the response of plasma delta 4-steroids to ACTH stimulation is comparable or higher than that in young subjects, whereas the response of delta 5-steroids is significantly decreased; estrogen treatment does not change this pattern. It is concluded that in elderly persons adrenal delta 4-steroid secretory capacity is unimpaired, whereas delta 5-steroid secretion is significantly decreased. The responsible mechanism remains to be elucidated.