Retinas of Royal College of Surgeons (RCS) rats were investigated immunocytochemically for the distribution of S antigen prior to and during the retinal disease process. RCS retinas onto which retinal pigment epithelium (RPE) had been transplanted were also immunostained with antibody for S antigen. At P2, weak immunostaining for S antigen was seen in neuroepithelium. At P22, the staining pattern outlined the entire photoreceptor layer. At P30, at the beginning of retinal degeneration, immunostaining for S antigen was considerably reduced in the degenerating photoreceptor outer segment. In the RCS retina at P90, immunostaining for S antigen was completely lost. However, retinas with transplanted RPE showed preserved immunocytochemical staining for S antigen at this late stage. These results suggest a loss of production of S antigen in degenerated retinal tissue, and that RPE transplantation helps to preserve S antigen in the RCS rat retina.