I have attempted to review the evidence that one or more immunopathologic mechanisms are responsible for the clinical and pathologic findings in multiple sclerosis (MS). I believe that there is considerable evidence for an immunopathogenesis of MS, but it is not clear what type or types of reactions are involved or against which autoantigen, neoantigen, or microbial antigen the reaction is directed. In addition, there is growing evidence that there are abnormalities in immunologic control mechanisms in patients with MS, although whether these changes are a cause or a result of the disease is not clear.