It was attempted to clarify the participation of K+-channels in the post-receptor mechanisms of the muscarinic and A1-adenosine receptor- mediated control of acetylcholine (ACh) release in the present study. Slices from the rat hippocampus were equilibrated with [3H]choline and the release of the labelled products was evoked by electrical stimulation (3 Hz, 5 V/cm, 2 ms, rectangular pulses), and the influence of various agents on the evoked tritium-outflow was investigated. Oxotremorine (Oxo, 0.1∼10 ՌM), a muscarinic agonist, and N6-cyclopentyladenosine (CPA, 1∼30 ՌM), a specific A1-adenosine agonist, decreased the ACh release in a dose-dependent manner, without affecting the basal rate of release. 4-aminopyridine (4AP), a specific A-type K+-channel blocker (1∼100 ՌM), increased the evoked ACh release in a dose-related fashion, and the basal rate of release is increased by 3 and 100 ՌM. Tetraethylammonium (TEA), a non-specific K+-channel blocker (0.1∼10 mM), increased the evoked ACh release in a dose-dependent manner without affecting the basal release. The effects of Oxo and CPA were not affected by 3 ՌM 4AP co-treatment, but 10 mM TEA significantly inhibited the effects of Oxo and CPA. 4AP (10 ՌM)- and TEA (10 mM)-induced increments of evoked ACh release were completely abolished in Ca2+-free medium, but these were recoverd in low Ca2+ medium. And the effects of K+-channel blockers in low Ca2+ medium were inhibited by Mg2+ (4 mM) and abolished by 0.3 ՌM tetrodotoxin (TTX). These results suggest that the changes in TEA-sensitive potassium channel permeability and the consequent limitation of Ca2+ influx are partly involved in the presynaptic modulation of the evoked ACh-release by muscarinic and A1-adenosine receptors of the rat hippocampus.