Conduction in demyelinated axons is characterized by decreased conduction velocity, temporal dispersion of impulses, and conduction failure. It is not possible to infer the electrical properties of the bared internodal axon membrane in demyelinated fibers from observations of decreased conduction velocity or conduction failure. Cytochemical evidence indicates that there are, in fact, distinct structural differences between nodal and internodal regions of the normal axon membrane. This conclusion is confirmed by freeze-fracture and pharmacological studies. A number of approaches to the development of effective symptomatic therapy in the demyelinating diseases are suggested by recent experimental findings: determination of the membrane properties necessary for conduction across focally demyelinated regions and the identification of agents that would encourage the development of these properties; alterations in the external milieu of demyelinated fibers; and the development of agents that might promote remyelination.