Lines of T lymphocytes reactive against the basic protein of myelin (BP) were found in previous studies to mediate experimental autoimmune encephalomyelitis (EAE) in rats. Moreover, inoculation of rats with attenuated anti-BP line cells vaccinated them against subsequent attempts to induce active EAE by injection of BP in adjuvant. In the present study, we investigated the effects of T lymphocyte lines reactive to different antigenic determinants on the BP molecule, they are the major encephalitogenic peptide (EP) determinant present on guinea pig BP (G-BP), and minor, non-EP determinants present on bovine BP (B-BP). We found that both lines of T lymphocytes could mediate EAE. Resistance to active EAE acquired by spontaneous recovery from line mediated EAE or by vaccination with attenuated cells, however, was found to be specific for the particular BP determinant. Thus, EAE may be mediated by lines of T lymphocytes reactive to different determinants on the BP molecule, but the resistance to EAE acquired by exposure to line cells is determinant specific. This suggests that acquired resistance to EAE is directed by the receptor specificity of the autoimmune anti-BP T cells.