beta-Dystroglycan (beta-DG) is a dystrophin-associated glycoprotein that is expressed in skeletal muscle and other tissues. In the retina, dystrophin is present in the outer plexiform layer (OPL), where it is enriched under the photoreceptor cell membrane. In this study we determined the immunocytochemical localization of beta-DG at both light and electron microscopic levels. beta-DG immunoreactivity was detected at the inner limiting membrane, OPL, and around blood vessels. Immunoelectron microscopy detected beta-DG immunoreactive products under the photoreceptor cell membrane, which are the same regions of dystrophin localization. In addition, beta-DG was detected under the Müller cell membrane that is attached to the paravitreous or perivascular basement membrane. Our results suggest that beta-DG may interact with dystrophin in photoreceptor membranes. However, beta-DG-related interactions between Müller cells and basement membranes appear to be independent of dystrophin and raise the possibility that beta-DG interacts with other molecules. We speculate that beta-DG plays a role in maintaining the structural relationship between photoreceptor and bipolar cells or between Müller cells and basement membranes.