In the aged rat, the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis was found to be increased. In fact, the plasma corticosterone concentrations in the aged (25 months) Sprague-Dawley rat were higher than in the young (3 months) Sprague-Dawley rat. To determine which component of the HPA axis principally contributes to this hyperactivity, an in vitro approach was applied. Neither the adrenal nor the pituitary revealed any age-induced modification in their basal or hormone-stimulated in vitro activity. Moreover, the ability of corticosterone to inhibit the in vitro stimulated pituitary adrenocorticotropic hormone release was preserved in aged rats. On the contrary, the in vitro hypothalamic activity was altered in aged rats. The basal and stimulated release of bioactive corticotropin-releasing factor were increased in aged rats. The results obtained in this study indicate that the hypercorticosteronemia of the aged Sprague-Dawley rat is associated with hypothalamic hyperactivity and with normal in vitro activity and reactivity of the adrenal and pituitary.