In vitro adrenal accumulation of cyclic 3´5´-adenosine monophosphate (cyclic AMP) and release of corticosterone in response to adrenocorticotropic hormone (ACTH), cyclic AMP or theophylline was assessed in 60- and 340-day-old male rats. Adrenal tissue from mature animals secreted significantly smaller quantities of corticosterone in response to ACTH, theophylline or cyclic AMP. Additionally, mature tissue accumulated significantly less cyclic AMP after treatment with ACTH or a combination of ACTH and theophylline. The data suggest an age-related refractoriness of adrenal cortical tissue to ACTH which may in part be related to decreased availability of and/or sensitivity to cyclic AM