Depolarizing afterpotentials (DAPs) were studied in intracellular recordings from neocortical slices bathed in tetrodotoxin (TTX) (1 microM) and tetraethylammonium chloride (TEA) (24 mM), to block voltage-dependent Na+ currents and most K+ currents. The DAP was Ca(2+)-dependent, in that its magnitude varied as a function of the duration of the preceding Ca2+ plateau. It had an apparent reversal potential of between -40 and -5 mV. The DAP was blocked when choline replaced all extracellular Na+; there was a hyperpolarizing shift in apparent reversal potential when extracellular Na+ was lowered. The DAP was blocked by amiloride (1 mM), which also decreased the preceding Ca2+ plateau. The data are consistent with the hypothesis that the DAP is due to electrogenic Na+/Ca2+ exchange.