We recently reported attenuation of autoimmune disease by low-dose gamma irradiation (repeated doses of 0.5 Gy) in MRL-lpr/ lpr mice. Here we studied the effect of low-dose gamma irradiation on experimental autoimmune encephalomyelitis (EAE), which is a rodent model of multiple sclerosis. SJL/J mice were immunized with myelin basic protein for the induction of EAE and were exposed to 0.5 Gy gamma rays once a week for 4 weeks. Radiation suppressed incidence and disease severity scores and delayed the onset of pathological changes. Pro-inflammatory cytokines (IFN-gamma and IL6), autoantibody and CD8+ cytotoxic T cells are involved in the appearance of EAE. Radiation suppressed the increases in these cytokines and the autoantibody production and blocked the increase in the population of CD8+ cytotoxic T cells. Production of IL17 by Th17 cells and/or gammadelta T cells, which plays a crucial role in EAE, was also significantly suppressed by radiation. Furthermore, a significant increase in regulatory T cells, which are involved in suppression of autoimmune disease, was found in irradiated EAE mice. These data suggest that low-dose gamma irradiation attenuates EAE through suppression of pro-inflammatory cytokines, reduction of cytotoxic T cells and induction of regulatory T cells.