Although the pathogenesis and mechanisms responsible for excessive connective tissue deposition are not known, it has been thought that specific growth factors may have an effect on scar formation by increasing the fibroblast population and by affecting the amount and types of matrix synthesized. In this regard, we explored the appearance and localization of TGFα, TGFβ PDGF, and sis-onc expression in situ. Sections of skin biopsies from eight scleroderma patients were investigated using specific antibodies to TGFα TGFβ human PDGF, and sis-onc products for immunohistochemistry. Most significantly, deposition of PDGF was detected in the endothelial lining of small capillaries in association with certain mononuclear cells of the perivascular infiltrates. In particular, strong labeling was observed in the cytoplasm of macrophages. Smooth muscle also appeared to be specifically labeled. Similarly, sis-onc product localized in the same areas. No significant staining was observed with antibodies to TGFα. TGFβ was found rather diffusely throughout the dermal connective tissue and was only occasionally observed in capillaries of lesions. We conclude that the PDGF may play an important role in the pathogenesis of scleroderma.