KGF is a fibroblast-derived member of the FGF family, with potent mitogenic activity on epithelial cells but no corresponding activity on fibroblasts, endothelial cells, melanocytes, or other nonepithelial targets of FGF action. Biochemical analysis established that KGF receptors bound aFGF with a high affinity but bFGF with at least an order of magnitude lower affinity. Expression cDNA cloning of a KGF receptor was accomplished by creation of a transforming autocrine loop. The full-length cDNA encoded a transmembrane, tyrosine kinase molecule which resembled the bFGF receptor encoded by flg, and was even more similar to the bek gene product. Future study will be aimed at determining differences responsible for the binding specificities that distinguish the KGF receptor from the bek and flg gene products. Using molecular probes to both KGF and its receptor to study their expression during development and in the adult should help define their role in normal growth and repair processes as well as possible pathologic roles in disease. This information, along with experiments testing the effects of KGF in vivo, could serve to identify situations in which KGF or antagonists to its actions would be of therapeutic benefit.