C58 mice are rendered susceptible to age-dependent polioencephalomyelitis by the natural aging process or by treatment with immunosuppressive agents. The mechanism of immunologically-mediated resistance was investigated. Susceptibility to the disease results from the loss of protective T cells. Transfer of unfractionated, naive splenic T cells from young donors prevented disease induction in immunosuppressed mice. Spleen cells from aged mice did not render young animals susceptible to disease, nor were they protective. Lyt phenotype analysis of the protective cells showed that the Lyt-1, Lyt-1,2, and Lyt-2 T cell subsets were all required for the generation of a protective response. When young donor animals were presensitized with LDV, transfer of Lyt-2 cells alone was protective.