The effects of aging on the stress response of the septo-hippocampal cholinergic neurons was assessed by monitoring hippocampal acetylcholine (ACh) release. Young (3-4 month old) and aged (23-24 month old) male rats were subjected to restraint stress for 1 h. ACh was elevated within 15 min of the onset of restraint stress (177.5% of basal level) in young rats but not in aged rats. Corticosterone concentration was significantly elevated by restraint stress in young rats but not in aged rats. The present results suggest that stress response of the septo-hippocampal cholinergic neurons and the hypothalamic-pituitary-adrenocortical axis is attenuated during aging.