Adult newts can regenerate their entire retinas following a complete removal of the original tissues. During retinal regeneration, ganglion cells differentiate first from the progenitor cells, and develop their capability of spike firing. In the present study, to understand the process of functional differentiation of ganglion cells, we investigated alterations of their voltage-gated sodium currents during retinal regeneration by a whole-cell patch-clamp technique. To minimize space clamp errors, sodium currents were recorded from neurite-free somata of presumptive ganglion cells that were mechanically isolated from living slices of regenerating retinas at different morphological stages. During retinal regeneration, the somatic sodium current density was increased 2.6-fold (48 to 123 pF/pA) and the half-activating voltage was shifted slightly to more hyperpolarizing membrane potentials (-10 to -13 mV), while steady-state inactivation was not changed obviously. Curve fitting analysis of currents revealed that the sodium current consists of two components with different inactivation time constants. During retinal regeneration, the ratio of slow to fast inactivating current component was increased 2.6-fold (0.11 to 0.29). These results suggest that the somatic sodium currents of ganglion cells may undergo modifications of their voltage dependence and kinetic properties during retinal regeneration. A small number of the presumptive ganglion cells in regenerating retinas with a segregating inner plexiform layer exhibited sodium currents comparable to those in the normal retina. This might suggest that maturational regulation of sodium channel function starts during a period of synaptic layer formation within the retina.