The pineal body of lower vertebrates is saccular and directly photoreceptive. The pineal gland of mammals is parenchymal and not directly photoreceptive. The parenchymal morphology of snake pineal raises questions of direct photoreceptivity of snake pineal and of correspondence of molecular homology with morphological homology. S-antigen and rhodopsin are highly conserved photoreceptor cell specific proteins. We used site-specific monoclonal antibodies (MAb) to study S-antigen and rhodopsin of snake pineal. Immunohistochemical reactivity of snake retina and pineal was compared to that of trout, guinea pig, and rat. MAb's to S-antigen reacted with each pineal and retina tested, but reactivity of individual MAb's with snake tissue was more similar to that with trout than with rat or guinea pig tissue. MAb's to rhodopsin did not react with snake pineal, although they did react with the photoreceptive trout pineal body. MAb's to rhodopsin reacted with retina of each species. These results suggest that although snake pineal is morphologically similar to mammalian pineal, and like mammalian pineal is probably not directly photoreceptive, it does have S-antigen homology with lower vertebrates such as trout.