OBJECTIVE To characterize the expression of transforming growth factor-alpha (TGF-alpha) in various histologic types of renal cell carcinomas. METHODS Immunohistochemistry of renal cell carcinoma and adjacent normal tissue was performed on formalin-fixed tissue using a specific monoclonal antibody to TGF-alpha. RESULTS Clear and distinct staining was present in normal distal convoluted tubules and collecting ducts. The growth factor was not observed in the glomerulus or the proximal tubule. In tumors composed of clear cells, staining was evident only in endothelial cells but not in the tumor cells themselves. In granular cell type tumors, the tumor cells as well as endothelial cells stained for TGF-alpha. When mixed cell type tumors were studied, a heterogenous pattern of growth factor expression was found. Endothelial cells and granular cells but not clear cells demonstrated positive staining. CONCLUSIONS These studies suggest that TGF-alpha is likely to play a major role in neovascularization of clear cell carcinomas and that the growth factor may be more important in supporting proliferation of granular cell type tumors.