The normal human retina and retinoblastomas were examined immunohistochemically to assess the localization of pineal antigens in the retina and the oncogenesis and differentiation of retinoblastoma. In the present study, 41 eyes excised from children (aged 4 months to 7 years, all unilateral occurrence) diagnosed to have retinoblastoma and 4 eyes with normal retinas, were used. Retinoblastomas were histopathologically classified into well-differentiated, moderately-differentiated, and poorly-differentiated types. The antibodies used were 9 monoclonal antibodies to human pineal antigens and 6 antibodies to neural tissues. In the normal retina, staining patterns characteristic of retinal cell layers were observed with PP1, PP3, PP5, PP6, PI1, and PI2 antibodies. In retinoblastomas, PP5 antibody, which reacts with horizontal cells and ganglion cells, and PP6 antibody, which reacts with part of the bipolar cells in the inner nuclear layer, showed intense staining in well-differentiated retinoblastomas, but the intensity of staining and the positivity decreased with the degree of dedifferentiation. Antigens recognized by PP3 and PP4 antibodies were positive in all retinoblanstomas. Reactions to GFAP antibody and antibodies that recognize Müller cells were negative. Retinoblanstomas may express markers of not only photoreceptor cells but also other retinal nuclear cells. These results suggest that the retinoblastoma might be developed from visual stem cells, which are common progenitor cells of photoreceptor cells, intermediate neurons, and ganglion cells.