In the present study the hypothesis was tested that in normal human aging an insensitivity of the glucocorticoid feedback signals is acquired. Thus, 40 healthy elderly (mean age: 69 +/- 5 years) and 20 younger (mean age: 34 +/- 8 years) individuals underwent a combined dexamethasone suppression/CRH-stimulation test. Cortisol secretion after dexamethasone (DEX) pretreatment and before CRH was increased in the older age group, but none of the subjects escaped DEX-induced suppression of cortisol. However, after additional CRH administration to the DEX-pretreated volunteers, the older group released significantly more cortisol than their young counterparts. Within the group of the elderly only, a positive correlation between BASAL, DEX-pretreated cortisol concentration and post-CRH steroid responses was found. Gender profoundly affected DEX/CRH-test outcome: females, regardless of age, had an increased hormonal secretion in comparison to males. It is concluded that, during human aging, adaptive changes in glucocorticoid receptors take place, allowing for the system to maintain "peripheral" glucocorticoid homeostasis, but that more sophisticated challenge procedures such as the DEX/CRH test reveal an age-related increase in HPA system activity.