Experimental autoimmune uveitis (EAU) can be induced in susceptible mice by immunization with retinal antigens. The response to uveitogens is genetically restricted. B10RIII and B10A mouse are highly susceptible to IRBP-induced uveitis, whereas B6 mouse is less susceptible. Immunization to B6 mouse with IRBP only induced very mild disease with low incidence. However, the susceptibility can be enhanced by transferring activated IRBP-specific T cells. In this study, we show that a reproducible and severe uveitis can be induced in B6 mice by adoptive transfer of IRBP-specific T cells. The disease incidence, severity, and duration can be readily controlled by the number and activation status of the injected T cells. Both CD4(+)- and CD8(+) IRBP1-20-specific T cells were identified in vitro IRBP peptide stimulation. In addition, IRBP1-20-specific T cells were consistently detected in recipient mice for up to 2 months, but only detected in the acute phase of the disease in actively immunized mice, indicating that persistency of injected IRBP1-20-specific T cells in recipient B6 mice might be one of the mechanisms causing chronic and severe disease. Giving that a large number of transgenic and KO mice are available in B6 background, an improved uveitis model in B6 mouse should assist the determination of pathogenesis of disease and identify molecules that can be targeted by new therapies.