The occurrence and histopathological characteristics of demyelination and neurodegeneration have been well described in different demyelinating mouse models. However, histopathological analysis is limiting in that it is unable to describe the functional consequences of demyelination and recovery after remyelination. Establishing the functional correlates of axon demyelination and remyelination is an important goal and can be used to measure axon function and develop neuroprotective therapies. This report describes a previously established, simple, easily applied method of electrophysiological measurement that can characterize white matter axonal dysfunction following demyelination and potential recovery after remyelination. It is designed to study in vitro stimulated compound action potentials in the corpus callosum of superfused brain slices at various time points and can be similarly used on white matter tracts in the optic nerve, spinal cord and cerebellum. Since behavioral testing can be performed prior to the brain slice electrophysiology, and the recorded slices can be post-fixed and subjected to histological analysis, correlates between behavior, axon function, and pathology can be determined. A temporal pattern of white matter functional deterioration and recovery can also be established to study mechanisms of demyelination-induced white matter injury and repair.