We have previously shown that (1) removal of extracellular sodium (Na + ) reduces the anoxia-induced depolarization in neurons in brain-slice preparations and (2) amiloride, which blocks Na + -dependent exchangers, prevents anoxic injury in cultured neocortical neurons. Since anoxia-induced depolarization has been linked to neuronal injury, we have examined in this study the role of Na + -dependent exchangers and voltage-gated Na + channels in the maintenance of membrane properties of CA1 neurons at rest and during acute hypoxia. We recorded intracellularly from CA1 neurons in hippocampal slices, monitored V m and measured input resistance (R m ) with periodic injections of negative current. We found that tetrodotoxin (TTX, 1 μM) hyperpolarized CA1 neurons at rest and significantly attenuated both the rate of depolarization (ΔV m /dt) and the rate of decline of R m (ΔR m /dt) by about 60% during the early phase of hypoxia. The effect of TTX was dose-dependent. Amiloride (1 mM) decreased V m and increased R m in the resting condition but changed little the effect of hypoxia on neuronal function. Benzamil and 5-(N-ethyl-N-isopropyl)-2 ,4 -amiloride (EIPA), two specific inhibitors of Na + dependent exchangers, were similar to amiloride in their effect. We conclude that neuronal membrane properties are better maintained during anoxia by reducing the activity of TTX-sensitive channels and not by the action of Na + -dependent exchangers.