Summary: Guinea pigs immunized with homologous retina in Freund's adjuvant developed both humoral and hypersensitive responses to retinal tissue, and were associated with production of experimental allergic uveitis in these animals. Serologic investigations indicated humoral antibody was made to two antigens of retinal specificity. One was extractable from retinal homogenate in saline, and the other was demonstrated in the particulate fraction of the ultracentrifuged homogenate. Antibodies to both antigens were produced by animals immunized with whole retinal emulsion, but a few of the animals made antibody to only one of the antigens. In these animals delayed hypersensitivity was elicited convincingly only to the extractable antigen. Following immunization with either soluble or particulate fraction of retina, guinea pigs made humoral antibody only to the fraction used for immunization. Delayed hypersensitivity was demonstrated only in animals immunized with the extract. The two antigens were limited in the guinea pig to retinal tissue, but similar antigens were demonstrated in the retinas of other species. Although humoral antibodies from guinea pigs immunized with homologous retina were reactive with heterologous retina, these animals showed delayed hypersensitivity only to guinea pig retina. Conversely, guinea pigs immunized with heterologous retina were not hypersensitive to homologous retina. These findings are correlated with previous observations that homologous, but not heterologous retina, was highly effective in production of experimental allergic uveitis in the guinea pig.