Demyelination and inflammation both contribute to the neurological deficits characteristic of multiple sclerosis and Guillain-Barré syndrome. Conduction deficits attributable to demyelination are well known, but it is becoming clear that factors such as nitric oxide, endocaine, cytokines, and antiganglioside antibodies also play significant roles. Demyelination directly affects conduction and also causes changes in both the distribution and repertoire of expressed axolemmal ion channels, which in turn affect impulse propagation and can promote hyperexcitability. In conducting axons, sustained trains of impulses can produce intermittent conduction failure, and, in the presence of nitric oxide exposure, can also cause axonal degeneration. Other factors impairing impulse transmission include nodal widening, glutamate toxicity, and disturbances of both the blood-brain barrier and synaptic transmission.