JO1784, a potent and specific sigma ligand, potentiated the KCl-evoked release of [3H]acetylcholine (ACh) from rat hippocampal slices superfused in vitro at 10 and 30 microM. This effect was stereospecific and was antagonized by the presence of haloperidol (0.3 microM). Under similar conditions, (+)-SKF 10,047 also had a potentiating effect whereas di-o-tolyl-guanidine had an inhibitory effect. Phencyclidine was devoid of activity up to a concentration of 30 microM. These results show that sigma compounds display differential effects on evoked [3H]ACh release in rat hippocampal slice preparations.