Current- and voltage-clamp techniques were used to analyze the mechanisms underlying the repolarization during N-methyl-D-aspartate (NMDA)-induced, tetrodotoxin-resistant pacemaker-like oscillations in lamprey spinal neurons. Long-lasting depolarizing current pulses (15-40 mV, 50-400 ms, tetrodotoxin and tetraethylammonium present) were followed by hyperpolarizing afterpotentials even when NMDA receptors were blocked, but they were markedly enhanced by application of N-methyl-D,L-aspartate (NM(DL)A). The afterpotentials were depressed by replacing Ca2+ with Ba2+. During voltage-clamp NM(DL)A enhanced a Ba2+-sensitive outward tail current following voltage steps of 15-40 mV. The outward current remained after injection of Cl-, as did the NMDA-induced membrane potential oscillations observed under current-clamp. These results suggest that the repolarization during NMDA-induced oscillations is due to Ca2+ entry both via NMDA-gated channels and conventional voltage-gated Ca2+ channels, leading to an activation of Ca2+-dependent K+ channels. The afterhyperpolarization following single action potentials, which is also due to Ca2+-dependent K+ channels, was not significantly altered by NMDA receptor activation, suggesting a different location of the Ca2+ entry during the two conditions in relation to the location of the activated Ca2+-dependent K+ channels.