In the CA1 region of rat hippocampal slices, the antiepileptic drug 2-phenyl-1,3-propanediol dicarbamate (felbamate; 100-1300 microM) concentration-dependently decreased extracellularly recorded synaptic potentials. The effect was significant at 200 microM, and became maximal at 700 microM felbamate, with a 70% decrease in population spike amplitude and 25% reduction of dendritic field excitatory postsynaptic potential (fEPSP) slope. Both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of the fEPSP were decreased by 700 microM felbamate. Up to 300 microM felbamate did not affect long-term potentiation (LTP), whereas 500 microM decreased the magnitude of LTP. Higher concentrations of felbamate (700-1300 microM) blocked induction of somatic and dendritic LTP completely, but reversibly. It appears that the concentrations of felbamate which affect LTP are higher than those needed for its antiepileptic action.