Long-term potentiation (LTP) was studied in CA1 neurons by tetanization of the Schaffer-commissural pathway in rat hippocampal slices. A brief tetanus (200 Hz for 1 s) caused an increase in amplitude of the population spike recorded from the CA1 area (typically about 200% of control), which lasted for more than 2 h. LTP was suppressed by perfusion of the muscarinic antagonist scopolamine (10(-5) M) from 5 min before to 15 min after the tetanus. If perfusion of the drug was begun after the tetanus, there was no affect on LTP. Scopolamine perfused without tetanus did not change the amplitude of the population spike. These results suggest that cholinergic system may affect the generation mechanisms of LTP.