Experimental autoimmune uveitis (EAU) is induced in rats by active immunization with retinal S-Antigen (S-Ag) in complete Freund's adjuvant. In contrast, oral administration of an antigen induces specific suppression. We investigated the potential of oral administration of S-Ag for the treatment of EAU. Prior to active immunization rats received 3 x 1 mg S-Ag orally. In contrast to untreated controls, the treated rats were significantly protected from EAU, as determined by clinical and histological examination. Lymphocytes from treated rats showed no proliferative response to S-Ag in vitro, but had a normal proliferative response to other antigens. CD8-positive T cells from S-Ag-fed rats inhibited the proliferation of an antigen-specific uveitogenic T-cell line in vitro. Moreover, the intensity of the inflammatory reaction to active immunization could be suppressed when feeding was started after the active immunization. These data show, that oral administration induced suppression, which provided significant protection from the development of uveitis.