The influence of melatonin on evoked potentials recorded from the CA1 field of mouse hippocampal slices was investigated. Melatonin (0.1–2.0 mM) and its analog, 6-chloromelatonin (0.1–0.5 mM) depressed evoked potentials (EPSP and the population spike) in a concentration-dependent manner. The melatonin-induced depression was followed by a slow recovery phase. Since the fiber potential was not affected, it was concluded that melatonin influenced synaptic efficiency and/or cell excitability. Luzindole, an antagonist of MT2 melatonin receptors, although slightly depressing evoked potentials when applied by itself (100 μM), blocked any further inhibition by melatonin when added afterwards. We concluded that melatonin reduced synaptic efficiency and/or excitability of hippocampal neurons most likely through interaction with MT2 melatonin receptors, but other possible mechanisms of melatonin action are also considered.