A noninactivating, persistent sodium current has been demonstrated previously in dorsal root ganglia neurons and in rat optic nerve. We report here that Na(+) channel blockade with tetrodotoxin (TTX) in isolated dorsal and ventral roots elicits membrane hyperpolarization, suggesting the presence of a persistent Na(+) current in peripheral axons. We used a modified sucrose-gap chamber to monitor resting and action potentials and observed a hyperpolarizing shift in the nerve potential of rat dorsal and ventral roots by TTX. The block of transient inward Na(+) currents was confirmed by the abolition of compound action potentials (CAPs). Moreover, depolarization of nerve roots by elevating extracellular K(+) concentrations to 40 mM eliminated CAPs but did not significantly alter TTX-induced hyperpolarizations, indicating that the persistent Na(+) currents in nerve roots are not voltage-dependent. Tetrodotoxin-sensitive persistent inward Na(+) currents are present in both dorsal and ventral root axons at rest and may contribute to axonal excitability.