Excitatory amino acid-induced responses were studied in cultured rat neocortical neurons using two types of whole-cell patch-clamp recordings. Conventional recording methods, using either KCl or CsCl in the patch pipet, showed N-methyl-d-aspartate (NMDA) currents to be biphasic, consisting of peak and steady-state currents with similar reversal potentials. Recordings obtained with the nystatin-perforated patch method and KCl as the principal intracellular cation disclosed an NMDA-evoked outward current. Outward currents were not seen with either recording method in response to kainate or quisqualate, nor in response to NMDA when CsCl was the major intracellular cation. The NMDA-evoked outward current is attributed to activation of a potassium current by calcium entering through the NMDA channel. This outward current may serve to limit neuronal depolarization during excessive NMDA-mediated excitation. © 1990.