Levetiracetam (LEV, 100mM) is one of the most important antieplieptic drugs. Although binding studies have shown that LEV interacts with the presynaptic vesicle proteine 2 A (SV2A), its mechanism of action remains unknown until now. Here, we used hippocampal slices of rat and human in order to study the electrophysiological effects of LEV on cells in the hippocampus and enthorhinal cortex at room temperature. Current clamp recordings in principal cells and interneurons show no effect of LEV on resting membraner conductance and action potential waveforms, input-output curves, afterhyper- or depolarising potentials or bursting patterns induced by short depolarizing current pulses. These data argue against a significant effect of LEV on voltage gated channels in the cell types studied here. Howeve, there was a reduction of both the amplitude and frequency of spontaneous inhibitory postsynaptic currents (spIPSCs) and the frequency of miniature IPSCs recorded in dentate gyrus granule cells. This effect was partially reversible and its timecourse compatible with the effects of LEV when applied in a clinical setting. Thus, this is the first report of an effect of Levetiracetam on synaptic transmission. As gabaergic inhibitory transmission is necessary to maintain interictal discharges this may reflect the effect of LEV on epilepticgenic neuronal networks.