The effect of transient cerebral ischemia on cholinergic metabolism was investigated in different brain areas of adult and young gerbils subjected to bilateral carotid artery occlusion for 15 min alone or with various times of recirculation. Tissue acetylcholine (ACh) and choline (Ch) levels were assessed by HPLC and electrochemical detection. Ischemia led to a significant decrease in tissue ACh and increase in tissue Ch levels, affecting to a lesser extent the young gerbils. Blood recirculation induced a rapid early restoration of the tissue ACh levels in young animals whereas a tremendous rebound of ACh was observed in the adult group. After 2 hr of reflow, Ch levels were normalized in adult brain and significantly reduced in the young brain. These findings represent the first comparative study demonstrating an age-dependent difference between young and adult animals in the susceptibility of cholinergic neurotransmission to cerebral ischemia.