Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) characterized by plaques of infiltrating CD4⁺ and CD8⁺ T cells. Studies of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, focus on the contribution of CD4⁺ myelin-specific T cells. The role of CD8⁺ myelin-specific T cells in mediating EAE or MS has not been described previously. Here, we demonstrate that myelin-specific CD8⁺ T cells induce severe CNS autoimmunity in mice. The pathology and clinical symptoms in CD8⁺ T cell–mediated CNS autoimmunity demonstrate similarities to MS not seen in myelin-specific CD4⁺ T cell–mediated EAE. These data suggest that myelin-specific CD8⁺ T cells could function as effector cells in the pathogenesis of MS.