Hippocampal pyramidal neurons express various extrasynaptic glutamate receptors. When glutamate spillover was facilitated by blocking glutamate uptake and fast synaptic transmission was blocked by antagonists of AMPA- and NMDA-type glutamate receptors and an ionotropic GABA receptor blocker, repetitive synaptic stimulation evoked a persistent membrane depolarization that consisted of an early Ca2+-independent component and a late Ca2+-dependent component. The early component, which we refer to as a plateau potential, had a half-width of 770 ± 160 ms and a steady peak level of −9.54 ± 3.50 mV. It was accompanied by an increase in membrane conductance, the I–V relationship of which showed a peak at −19.91 ± 2.18 mV and reversal of the current at −4.32 ± 2.13 mV, and was suppressed by high concentration of an NMDA receptor (NMDAR) antagonist d-APV, or an NMDAR glycine-binding site antagonist 5,7-dCK. After blocking synaptically located NMDARs using MK801, the potential was still evoked synaptically when spillover was facilitated. A sustained depolarization was evoked by iontophoretic application of glutamate in the presence or absence of a glutamate uptake blocker. This potential was not affected by Na+ or Ca2+ channel blockers, but was suppressed by 5,7-dCK, leaving an unspecified depolarizing potential. Iontophoresis of NMDA evoked a sustained depolarization that was blocked by a high concentration of d-APV or 5,7-dCK. The I–V relationship of the current during this potential was similar to that obtained during the synaptically induced plateau potentials. These results show that CA1 pyramidal neurons generate plateau potentials mediated most likely by activation of extrasynaptic NMDARs.