S-antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU) in rats can be suppressed by injecting the mouse monoclonal antibody (mAb) S2D2 or a polyclonal rat anti-idiotype S2D2 (anti-Id S2D2) antibody, the internal image of the epitope of S-Ag recognized by mAb S2D2. This epitope located in amino acids 40–50 of bovine S-Ag (peptide S2), displays an homology with a sequence of human tumor necrosis factor alpha (hTNFα) (peptide RRAN) which is also recognized by S2D2. (Stiemer et al., this symposium). We show that one injection of S2D2 at the time of immunization with S-Ag suppressed EAU and modulated the production of antibodies against peptides of bovine or human S-Ag containing the S2 epitope and against peptide RRAN. Immunization against anti-Id S2D2 stimulated antibody production to peptide S2 and RRAN and inhibited EAU. These data suggest that disease suppression could be related to the production of antibodies against the S-Ag/TNFαcommon epitope.