The concept of autoimmune myelinopathy as the primary pathology in multiple sclerosis (MS) is problematic. Vasculitis is seen in the MS brain, both within lesions and in adjacent normal-appearing white matter. The first observation in acute relapse is the sudden, orderly death of oligodendrocytes; inflammatory removal of unsupported myelin seems to be a secondary process. An alternative explanation for these findings is that oligodendrocyte infection might trigger an inflammatory response. Many pathogens, including Chlamydophila (Chlamydia) pneumoniae, have been associated with MS. MS might be an infectious syndrome in which C. pneumoniae has a role in a subset of patients. Mechanisms by which such a cryptic infection could engender relapsing-remitting and, ultimately, progressive disease patterns are discussed.