PHOSPHORYLATION Of glutamate receptors is probably an important mechanism for modulating excitatory transmission(1-4). However, there is little direct evidence to indicate which protein phosphatases can dephosphorylate glutamate(5) or other ligandgated channels(6), although it is known that protein phosphatases 1 and 2A play a major part in modulating voltage(7-10) and second-messenger-gated channels(11). Here we report that in cultured hippocampal neurons, the N-methgl-D-aspartate (NMDA) receptor can be regulated by endogenous and exogenous serine/threonine protein phosphatases. Phosphatase inhibitors enhanced NMDA currents recorded using the perforated patch technique(13) or in cell-attached patches, whereas protein phosphatases 1 or 2A decreased the open probability of these channels in inside-out patches.