Transforming growth factors (TGFs)-alpha and -beta are regulatory polypeptides that reversibly confer a transformed phenotype upon normal cultured fibroblasts. TGF-alpha is synthesized primarily by malignant cells and shares many properties with the tissue mitogen, epidermal growth factor (EGF). The expression of TGF-beta mRNA has been demonstrated in a variety of normal and malignant cell types, some of which secrete the mature protein in an inactive form. To investigate the role of TGFs in human renal cell carcinoma (RCC), we used two renal tumor-derived cell lines and one established RCC cell line for analysis of TGF-alpha and TGF-beta mRNA production and for evaluation of TGF-beta protein secretion. By northern blot hybridization, all three RCC cell lines expressed TGF-alpha and -beta mRNA. In addition, TGF-beta activity was found in the conditioned medium from these cells. The secreted TGF-beta protein, however, displayed biological activity only after activation by acid-treatment. These data demonstrate the constitutive expression of TGF-alpha and -beta mRNA by RCC cell lines and, also, the secretion by this tumor of endogenous TGF-beta protein in a latent form.