T cells expressing the alpha beta T-cell receptor (TCR) for antigen can elicit anti-idiotypic antibodies specific for the TCR that regulate T-cell function. Defined sequences of the TCR, however, have not been used to elicit specific antibodies and the role of cellular immunity directed against TCR determinants has not been studied. We immunized Lewis rats with a synthetic peptide representing a hypervariable region of the TCR V beta 8 molecule. Subsequent induction of experimental autoimmune encephalomyelitis, a paralytic disease of the central nervous system mediated primarily by V beta 8+ T cells specific for myelin basic protein was prevented. T cells specific for the TCR V beta 8 peptide conferred passive protection against the disease to naive rats, apparently by shifting the predominant T-cell response away from the major encephalitogenic epitope of basic protein. This is the first report demonstrating the use of a synthetic TCR V-region peptide to induce specific regulatory immunity and has important implications for the regulation of human disease characterized by common TCR V-gene usage.