PROTEIN kinases modulate the activity of several ligand-gated ion channels¹, including the NMDA (N-methyl-D-aspartate)² subtype of glutamate receptor. Although phosphorylation and dephosphorylation of glutamate receptors may participate in several lasting physiological and pathological alterations of neuronal excitability^3–7, the physiological control of this cycle for NMDA channels has not yet been established. Using cell-attached recordings in acutely dissociated adult rat dentate gyrus granule cells, we now demonstrate that inhibitors of an endogenous serine/threonine phosphatase prolong the duration of single NMDA channel openings, bursts, clusters and superclusters. Okadaic acid, a non-selective phosphatase inhibitor, prolongs channel openings only at a concentration that inhibits the Ca²⁺/calmodulin-dependent phosphatase 2B (calcineurin)⁸, and is ineffective when Ca²⁺ entry through NMDA channels is prevented. Furthermore, FK506, an inhibitor of calcineurin^9,10, mimics the effects of okadaic acid. Thus in adult neurons, calcineurin, activated by calcium entry through native NMDA channels, shortens the duration of channel openings. Simulated synaptic currents¹¹ were enhanced after phosphatase inhibition, which is consistent with the importance of phosphorylation of the NMDA-receptor complex in the short- and long-term control of neuronal excitability.