Experimental autoimmune uveitis (EAU) was observed in Hartley guinea pigs following Immunization with two small synthetic peptides, peptide M and peptide M15L, which correspond to the amino acid sequence of a well-characterized region of bovine S-antigen. Groups of guinea pigs were immunized with 100γg of each peptide in complete Freund's adjuvant and examined at regular intervals for the development of disease. Approximately two weeks later, an EAU was present which was characterized clinically by iris and pericorneal hyperemia. Histopathologically, a severe inflammatory response involving the uveal tract and retina was observed. In these eyes the photoreceptor cell layer of the retina was destroyed. A subretinal exudate containing mononuclear cells and polymorphonuclear leukocytes was also present. In addition, animals with EAU showed an associated pinealitis characterized by a lymphocytic infiltration of the subcapsular and central area of the pineal gland. Furthermore, draining lymph node cells of guinea pigs immunized with peptide M showed strong in vitro proliferative responses towards peptide M as measured by3H thymidine uptake. These results demonstrate the existence of at least one common pathogenic epitope in bovine S-antigen for the induction of EAU in Hartley guinea pigs and Lewis rats.