Withdrawal from chronic ethanol administration results in hyperexcitability. In the hippocampus, evoked bursting activity and spontaneous epileptiform events are seen. The present study investigated the effect of ethanol withdrawal on N-methyl-D-aspartate (NMDA) receptor-mediated postsynaptic potentials and on voltage-gated calcium currents, in mouse hippocampal pyramidal cells. The NMDA receptor-mediated component of synaptic excitation was increased during withdrawal, accompanied by an increase in synaptic activation of calcium spikes. Evidence for a direct effect of ethanol withdrawal on calcium channel function was seen in voltage clamp recordings of isolated, slowly inactivating calcium currents. A synergistic effect of increased NMDA receptor and calcium channel function is therefore suggested to contribute to hyperexcitability during ethanol withdrawal.