Experimental allergic uveitis (EAU) was produced in strain 13 guinea pigs after immunization with purified guinea pig retinal rod outer segments and pigment epithelium (PE) in mycobacterial adjuvant emulsion, The lesions of EAU appear as inflammatory infiltrates of the iris, ciliary body, and choroid, often with photoreceptor degeneration. Specific antibodies are frequently detected in the serum of some but not of all animals with clinical uveitis. Immunohistochemical staining of normal and inflamed eyes with serum from the immunized animals with clinical disease demonstrated specific antigens localized in the retinal photoreceptor layers, whether or not circulating precipitating antibodies were also present in the serum. All immunized animals demonstrated delayed-type hypersensitivity (DTH) characterized by skin reactions of mononuclear cells and by the in vitro inhibition of migration of cells from the sensitized animals in the presence of specific antigen whether or not clinical uveitis occurred. However, stronger DTH reactions were observed during clinical uveitis. Cellular immunity appears to correlate with clinical EAU, whereas, no correlation was found with serum antibody. These findings suggest that the retinal photoreceptor cell and PE are the source of the significant antigens in autoimmune uveitis and retinitis.