Voltage-gated sodium channels are largely localized to the nodes of Ranvier in myelinated axons, providing the physiological basis for saltatory conduction. Studies using antisodium channel antibodies have shown that along demyelinated axons sodium channels form new distributions. The nature of this changed distribution appears to vary with the time course and mechanism of demyelination. In chronic demyelination, sodium channels increase in number and redistribute along previously internodal axon segments. In chronic demyelination produced by doxorubicin, the increase in sodium channels appeared independently of Schwann cells, suggesting increased neuronal synthesis. In acute demyelination produced by lysolecithin new clusters of sodium channels developed but only in association with the edges of remyelinating Schwann cells, which appeared to control the distribution and mobility of the channels. These findings affirm the plasticity of sodium channels in demyelinated axons and are relevant to understanding how these axons recover conduction.