An experimental model of inflammatory eye disease, experimental autoimmune uveitis (EAU), was established by injecting rats in the footpad with S-antigen in complete Freund's adjuvant. This model system was used to evaluate the role of major histocompatibility complex (MHC) class II antigens (Ia) in the pathogenesis of this T cell mediated disease. One day prior to S-antigen priming, rats were injected with either anti-Ia antibodies or with mouse ascites. Clinical and histopathological analysis of eyes from rats treated with anti-Ia antibody showed less ocular inflammation as well as a delay in onset of EAU when compared to controls (p = 0.01). Furthermore, immunocytochemical evaluation demonstrated that tissue obtained from animals receiving anti-Ia therapy also expressed less Ia antigen, as well as a diminution in the number of infiltrating macrophages and lymphocytes. These data show that anti-Ia treatment significantly modifies the course of EAU in the rat. In addition, this study suggests that MHC class II antigen expression may be involved in the initiation and continuation of immune responses that results in ocular inflammatory diseases.