The effects of calorie restriction, exercise, and aging on the pituitary-adrenal axis were studied in male Wistar rats from 12 to 28 months of age. There were 4 experimental groups: sedentary, ad libitum fed (A); sedentary, diet restricted by feeding on alternate days (R); exercised by swimming on alternate days, ad libitum fed (AE); exercised as AE, diet restricted as R (RE). Pituitary-adrenal function was assessed by measuring serum ACTH and corticosterone concentrations, adrenal weight, hepatic glucocorticoid receptor concentration, and hepatic tyrosine aminotransferase (TAT) activity. Serum corticosterone concentration increased with age while serum ACTH decreased from 12 to 20 months of age and then increased thereafter. TAT activity decreased and receptor concentration remained constant with age. Adrenal weights increased with age; those of AE rats increased dramatically. Analyses for relationships between variables revealed a quadratic relationship between serum ACTH and corticosterone concentrations. There tended to be an inverse relationship between TAT activity and corticosterone concentration. These observations may be indicative of a loss of feedback loop integrity with aging. Neither calorie restriction nor exercise were able to maintain the integrity of pituitary-adrenal function during aging, though dietary restriction did slow age-associated decrements of TAT activity.