A change in the response of neocortical neurons to N-methyl-d-aspartate (NMDA) was observed during the first 2 weeks of postnatal development. When NMDA was bath applied, the membrane current-voltage relationship recorded in neurons from postnatal day (PN) 3-5 rats displayed a region of decreased inward current at hyperpolarized membrane potentials. By PN 9-14, the net inward current at hyperpolarized potentials was significantly less than that recorded in PN 3-5 neurons. These results indicate that a developmental increase in the voltage-dependence of NMDA responses exists, which may be due to changes in magnesium sensitivity of the NMDA receptor. © 1994.