We studied the effect of high-dose mouse IgG on TMEV-induced demyelinating disease (TMEV-IDD). We injected TMEV intracerebrally into susceptible SJL/J mice and induced TMEV-IDD. Mouse IgG were injected intraperitonealy, and clinical course and various immunological indicators were studied. The results show that TMEV-IDD was significantly suppressed both clinically and histologically (P<0.01) when IgG were administered in the effector phase. The delayed type hypersensitivity and T cell proliferative response specific for TMEV were decreased by this treatment. In an ELISPOT assay, the number of TNF-alpha producing lymphocytes in the spinal cords was low in high-dose IgG treated mice compared with PBS treated control mice. These data suggest that administration of IgG suppresses TMEV-IDD and may be promising treatment to prevent exacerbation of human multiple sclerosis.