Theiler’s murine encephalomyelitis virus (TMEV) is a single-stranded RNA virus that belongs to the family of picornaviruses. Intracranial inoculation of susceptible mouse strains with TMEV results in biphasic disease, consisting of early acute disease that resembles poliomyelitis, followed by late chronic demyelinating disease that is characterized by the appearance of chronic inflammatory demyelinating lesions. Susceptibility to TMEV infection is genetically controlled by three loci: one that maps to the H-2D region of the major histocompatibility complex, one to the beta-chain constant region of the T-cell antigen receptor, and one located on chromosome 3. Both early acute and chronic late demyelinating diseases are immunologically mediated. T cells appear to play an important role in the pathogenesis of the disease. TMEV-induced demyelinating disease in mice has extensive similarities with multiple sclerosis, and it is considered one of the best experimental animal models for multiple sclerosis.