This laboratory has determined amino acid sequences of human, mouse, and bovine retinal S-antigen and rat pineal gland S-antigen. Immunogenic sites and four uveitopathogenic sites of S-antigen were also determined. Many proteins in the National Biomedical Research Foundation data base have similar sequences with uveitopathogenic site. We induced EAU and pinealitis in Lewis rats with a small synthetic peptide from yeast (Saccharomyces cerevisiae) histone H3, which contains five consecutive amino acids identical to a uveitopathogenic site in human S-antigen. Synthetic peptides of proteins from potato proteinase inhibitor, hepatitis virus, Moloney murine sarcoma virus, and Moloney murine leukemia virus also induced EAU. In addition, native yeast histone H3 was capable of inducing EAU. These findings provide a basis for understanding human autoimmune inflammatory diseases of the eye.