I have attempted here to outline the basic biochemical knowledge that we have now secured on the EGF family of proteins. In the future we will learn much more about the differential role of EGF versus TGF-alpha, about the physiological significance of amphiregulin, the newest member of this family, and about the roles of TGF-alpha and amphiregulin in cancer. Many questions remain. What is the importance of these factors in embryogenesis and fetal development? Is there an involvement of the EGF-like domains of extracellular proteins in cell-to-extracellular-matrix interactions? Do these extracellular matrix EGF-like entities function in a similar manner to fibroblast growth factor in cell growth and in mediating the relationship of cells to the extracellular matrix? What is the significance of cell membrane-bound forms of EGF and TGF-alpha as potential cell-to-cell contact regulators? What is the role of the viral EGF-like proteins in the viral infective and transforming process? These and other questions will be addressed in the next decade. The key question has already been well stated: 'what is the normal physiological role of EGF during development and homeostasis? The answers to these and a host of other questions must be found before we can fully comprehend this important regulatory system' (Cohen, 1987).