Using in vivo microdialysis, cortical acetylcholine (ACh) efflux was measured in freely moving Brown Norway/Fischer 344 F1 rats, aged 4 or 22 months. The effects of local, intracortical perfusion of atropine (1.0 or 100.0 microM) via the dialysis probe were compared to local K+ (100.0 mM) stimulation in the presence of elevated extracellular Ca2+ (2.5 mM). Basal cortical ACh efflux in aged rats was similar to that of young animals. Administration of atropine (1.0 or 100.0 microM) via the cortical dialysis probe substantially increased cortical ACh efflux, but did not differentially stimulate ACh efflux in young and aged rats. In contrast, ACh efflux stimulated locally with K+ and Ca2+ was significantly reduced in aged rats relative to young adults. The implications of the dissociable effects of K(+)-depolarization and muscarinic blockade for local regulation of cortical ACh efflux in aged animals are discussed.