This study compared plasma concentrations of adrenocorticotropin (ACTH) and cortisol in young men (N = 10, mean age 24.4 years), young women (N = 10, mean age 25.4 years), old men (N = 8, mean age 81.6 years) and old women (N = 8, mean age 83.5 years) under basal resting conditions and after stimulation with either human corticotropin-releasing hormone (hCRH, 100 mu g iv) or a combined injection of hCRH (100 mu g) and arginine vasopressin (VP, 0.5 IU iv). Basal secretion of cortisol did not differ among groups, but basal concentrations of ACTH were diminished in young women (p < 0.01), indicating an enhanced adrenal sensitivity to ACTH in these subjects. Pituitary responses to hCRH did not differ between young men and women, However, responses to hCRH/VP were stronger in the young females (p < 0.01), suggesting an enhanced pituitary responsiveness to the augmenting effect of VP on ACTH release in this group, Pituitary-adrenal secretory responses were greater in old than in young men after sole injection of hCRH (p < 0.05) and even more so after combined injection of hCRH/VP (p < 0.01), In old women, pituitary-adrenal secretory responses were also greater than in young women (p < 0.05). But, in particular for responses to hCRH/VP, these effects were less distinct; than within the men. Results indicate an enhancing effect of age on pituitary responsiveness to the hypothalamic secretagogues hCRH and VP, modulated by the subject's gender.