Retinal S-antigen is widely used to study the LEW rat model of experimental autoimmune uveoretinitis (EAU). In this report, we have examined the T cell receptor V gene usage of several T cell lines recognizing either pathogenic or nonpathogenic sites on S-antigen to determine whether the Vα510 and Vβ510 rat homologues of the murine Vα2 and Vβ8 families, respectively, are used by uveitogenic T cells. Using cDNA probes for a LEW rat T cell receptor specific for the encephalitogenic determinant of myelin basic protein, we have found that in the retinal S-antigen/EAU model for autoimmune disease, pathogenicity correlates with usage of those rat V genes. Thus, all of the pathogenic lines were found to express T cell receptors of the Vβ510 and Vα510 families; conversely, Vβ510 usage was not detected in any of the nonpathogenic lines. Usage of these V regions has been associated with pathogenicity in the murine and rat models of experimental autoimmune encephalomyelitis, and now with S-antigen-induced EAU.