Transforming growth factor-ß(TGF-ß) is a multifunctional growth factor that can either stimulate or inhibit cellular proliferation depending on cell type and culture conditions. The immunohistochemical localization of TGF-ßwas investigated in human retinas and choroids using streptavidin peroxidase immunohistochemistry and a polyclonal rabbit antibody directed against the N-terminal 30 amino acids of TGF-ß1. This antibody recognizes theß1 form of TGF-ßbut notß2. TGF-ßlocalization was observed exclusively in photoreceptors in all adult non-diabetic and non-insulin dependent diabetic eyes, and 4 of 6 insulin dependent eyes. It was determined that TGF-ßwas associated with both rods and cones using localization of peanut agglutinin(PNA), a lectin which binds to cone sheaths, on serial sections. Chondroitinase ABC digestion of sections prior to immunohistochemistry did not reduce TGF-ßimmunoreactivity, suggesting that binding was not to glycosaminoglycans in the interphotoreceptor matrix.TGF-ßimmunoreactivity was not observed in 2 premature human eyes in which photoreceptor outer segments had not yet developed. Localization in photoreceptors was also not observed in photocoagulation scars, in atrophic regions in a diabetic retina, nor in detached areas of retina from a young victim of head trauma. Based on PNA binding, succinate dehydrogenase enzyme histochemistry and phase contrast microscopy on adjacent sections, the TGF-ßnegative areas of these retinas did not appear to have viable photoreceptors.This work demonstrates that TGF-ßis found exclusively in viable adult human retinal photoreceptors. It's function in these cells is currently not known.