Aging is associated with alterations in mood, thermoregulation, pain threshold, and stress response. Because these functions may be modulated by endogenous opiates, we measured immunoreactive ACTH and β-endorphin in discrete brain areas and pituitary glands from rats aged 6 weeks (young), 6 months (mature), and 20–24 months (senescent). β-Endorphin and ACTH declined significantly with aging in the hypothalamus and corpus striatum. β-Endorphin and ACTH increased in the frontal lobe during early life; however, no change was noted after maturity. A discordant response with age was noted in the pituitary in that ACTH did not change, while β-endorphin increased early in life without change after maturity. Cerebellar tissue exhibited no immunoreactive ACTH or β-endorphin. Age-related changes in brain and pituitary β-endorphin and ACTH must be considered in the evaluation of the physiological aging process and when comparing studies of these neuropeptides.