Vision is a highly complex process common to many vertebrate and invertebrate species. The visual system of Drosophila represents a valuable model in which to study this process since its chromosomal makeup has been well mapped and many mutants containing specific photoreceptor defects have been described. S-antigen is a well-characterized photoreceptor cell protein which plays a fundamental role in the visual process. In this study, we used a panel of four monoclonal antibodies (MAbs) specific for amino, mid and carboxy terminal amino acid sequences in S-antigen in order to examine S-antigen immunoreactivity in the Drosophila visual system. Two MAbs, MAb5C6.47 and MAbC10-C10, localized S-antigen to the retinules and ocelli. In contrast, MAbA2-G5 and MAbA9-C6 did not stain. The presence and strong antigenic similarity of an S-antigen homolog in Drosophila suggests that in both vertebrates and invertebrates S-antigen plays a major role in the regulation of the phototransduction of vision.