Excitatory postsynaptic currents (EPSCs) were recorded in pyramidal neurons of layer 2/3 somatosensory cortex, in the slices from the brains of 17 - 22 day old mice. Each episode of low frequency stimulation at -80 mV caused strong inhibition of the NMDA component of the EPSC, measured either at -40 or +40 mV. The inhibition of NMDA current was eliminated by PPADS, and attenuated by intracellularly applied BAPTA, suggesting that NMDA receptors were inhibited by calcium entry through P2X receptors. Direct application of P2X receptor agonists to the cortical slice also caused the inactivation of NMDA receptors. When ATP was applied at -80 mV the NMDA receptor-mediated EPSCs were inhibited by 40–60 %, whereas ATP application at +40 mV failed to affect NMDA EPSCs. Taken together these results suggest that postsynaptic P2X receptor can control the activity of NMDA receptors via-calcium dependent mechanism. This may imply a specific modulatory role for the purinergic component in the excitatory synaptic transmission.