S-antigen (S-Ag), a well characterized 45-kDa protein in the photoreceptor cells, induces predominantly T-cell-mediated autoimmune uveitis when injected into experimental animals. Recently, we have shown that native histone H3 protein derived from yeast (Saccharomyces cerevisiae), or a synthetic peptide that is homologous with S-Ag peptide M in having six consecutive amino acids, induces experimental autoimmune uveitis (EAU) similar to that induced by native S-Ag in the Lewis rat. In this study, monkeys (Macaca fascicularis) immunized with histone H3 peptide developed a strong cellular immune response to this peptide as well as to peptide M. However, no significant inflammation or hypervascularization was observed in the retina or the iris during the experimental period, when they were examined clinically with an inverted ophthalmoscope. Histopathological examination showed that all monkeys injected with histone H3 peptide or with native histone H3 lost a large number of photoreceptor rod cells and developed neovascularization in the outer nuclear cell layer of the retina. These histopathological findings in the monkey retina closely resemble those seen in human patients with some types of uveitis. The possible involvement of microbial proteins having sequence homology with normal retinal proteins in the pathogenicity of human uveitis is discussed.