The mechanism by which anoxia blocks impulse conduction was studied in isolated sciatic nerves from the rat. The desheathed nerve was mounted in a recording chamber, and the compound action potential (CAP) was measured at controlled temperature (23 and 37 degrees C). When the nerve was irrigated with nitrogenated Ringer's solution compound action potential decreased to 50% in 10 min at 37 degrees C and in 35 min at 23 degrees C, whereas in oxygenated solution compound action potential decreased less than 5% in 60 min. A Na-free nitrogenated solution similarly caused anoxic block, that is the effect was independent of impulse activity. Ouabain (1 mM) decreased compound action potential by only ca. 4% in 30 min, and the effect of anoxia was delayed in presence of ouabain. Dinitrophenol (0.05 mM) reduced compound action potential to 50% in 5 min. These findings indicated that the anoxic block was not related to changes in axonal concentration of Na or K following impulse activity or inhibition of Na-K-ATPase. Instead the findings imply that the anoxic block is due to inactivation of Na-channels as a consequence of inhibition of another ATP-dependent process in the axon.