In contrast to tonic, extrasynaptic GABAA receptor-mediated signaling, the physiological significance of tonic, extrasynaptic NMDA receptor (NMDAR)-mediated signaling remains uncertain. In this study we have used memantine, a reversible open channel blocker of NMDARs, as a tool to examine tonic NMDAR-mediated signalling in rat hippocampal slices. Memantine in a concentration of 10 mM (considered equivalent to the higher end of clinically relevant doses used to treat symptoms in Alzheimer's disease) had no effect on synaptically evoked NMDAR-mediated responses in either pyramidal neurons, or in GABAergic interneurons. On the other hand, 10 mM memantine reduced tonic NMDAR-mediated currents in GABAergic cells by about 50 %. We further found that interneurons had larger tonic NMDAR- mediated currents than had pyramidal neurons. These tonic NMDAR-mediated currents in interneurons contributed significantly to the excitability of the interneurons since 10 mM memantine reduced the disynaptic IPSC in pyramidal neurons. Moreover, memantine increased the magnitude of the population spike, likely primarily because of disinhibition. Our results suggest that tonically active extrasynaptic NMDA receptors contribute to intrinsic excitation, particularly in interneurons, and that these NMDA receptors are specifically targeted by low dosages of the NMDA receptor open channel blocker memantine.