JORMA KESKI-OJA Two types of transforming growth factors (TGF) have been purified and well characterized, TGFa and TGFP. TGFa is a 5.6 kD single chain molecule that shows sequence homology to epidermal growth factor (EGF), binds to the EGF receptor, and has biological effects very similar to those of EGF. TGFP is different from TGFa in its molecular structure and biological activity, and has its own specific cell surface receptor. TGFP is a 25 kD hornodimer of 12.5 kD subunits that shows no sequence homology to TCFa. TGFP is a highly ubiquitous molecule produced by a variety of cell types in an inactive form. Most cells have receptors for TGFP, suggesting that a major regulatory step in TGFP action is through activation of the iuactive form. Growth stimulatory effects with TGFP have been observed so far only in fibroblastic cells. In at least one circumstance, there is evidence that the stimulatory effects of TGFP in fibroblastic cells is indirect through induction of c-sis and autocrine stimulation by platelet-derived growth factor (PDGF)-like material. TGFP inhibits in vitro proliferation of most cell types tested, including normal epithelial cells. Thus TGFP is primarily a growth inhibitor and not a classical growth factor. Increased autocrine stimulation by endogenous TGFP in fibroblastic cells or decreased inhibitory effects in epithelial cells (or other cells normally inhibited by TGFP) could lead to an increased proliferative potential and thereby contribute to the neoplastic phenotype.