Severe murine experimental autoimmune neuritis (sm-EAN) in SJL/J mice is a recently described, but incompletely characterized mouse model of Guillain-Barré syndrome (GBS). Electrophysiological and pathologic characterization during the disease course is a necessary prerequisite to designing mechanistic studies that may be relevant to GBS pathogenesis. Sm-EAN is a monophasic disorder with electrophysiological evidence for a diffuse demyelinating polyneuropathy with axonal loss at peak severity. Regression analyses demonstrated strong correlations between neuromuscular severity scores and electrophysiological parameters during the disease course. Progressive multi-focal or diffuse demyelination with axonal loss was observed pathologically in sciatic nerves in association with mononuclear cell infiltrates (F4/80+ macrophages > CD3+ T-lymphocytes > CD19+ B-lymphocytes), peaking at maximal severity. Regression analyses demonstrated strong correlations between severity scores and inflammatory cell counts. The correlative data imply that mononuclear infiltration, as well as demyelination and axonal loss are directly related to the observed neuromuscular weakness in sm-EAN. The high induction rates, as well as pathologic similarities with AIDP make sm-EAN a robust model to study the pathogenesis of human peripheral nerve inflammation using objective outcome measures. © 2009 Elsevier B.V.