We studied the kinetics of recovery from inactivation of voltage-dependent Na+ channels in rat hippocampal CA1 neurons. Recovery proceeded exponentially after an initial delay and was accompanied by a tiny ionic current. Both thedelay and thetimeconstant of recovery became shorter with increasing hyperpolarization. Negative to-170 mV, the rate of recovery saturated at-4 ms-’(22X). Recovery from block by the anticonvulsant drug diphenylhydantoin was far slower, but the pattern of voltage dependence was very similar. Our results suggest that, analogous to the coupling between Na+ channel activation and the development of inactivation, recovery from inactivation is coupled to channel deactivation. Such coupling ensures very little “leak” Na+ current during recovery and a highly voltage-sensitive re priming of Na+ channels for the next impulse.