Superfused slices of human neocortex, prepared from surgically removed tissue (to gain access to subcortical tumors) and prelabelled with [3H]choline, were stimulated electrically to evoke action potential-induced, exocytotic [3H]acetylcholine release. For comparison, rat cortex slices were also used. [3H]ACh release decreased with the age of the patients and was modulated by muscarinic autoreceptors and by 5-hydroxytryptamine1F, neurokinin1, and kappa-opioid receptors located on cholinergic terminals. In addition, 5-hydroxytryptamine2 and delta-opioid receptors located on interneurons were also involved in the modulation of [3H]ACh release. The present findings might help to explain pathological conditions in Alzheimer's disease.