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Polypeptide growth factors are important effectors of cell growth and differentiation in vitro and are thought to be critical for processes such as specification of cell fate, tissue growth and organogenesis in vivo. Scatter factor/hepatocyte growth factor (SF/HGF) is the prototype of an emerging family of growth factors that resemble in their domain structure and mechanism of activation the blood proteinase plasminogen. The cellular responses of SF/HGF are mediated by the c-Met tyrosine kinase receptor. Here we report that mice lacking SF/HGF fail to complete development and die in utero. The mutation affects the embryonic liver, which is reduced in size and shows extensive loss of parenchymal cells. In addition, development of the placenta, particularly of trophoblast cells, is impaired. Thus, SF/HGF is essential for the development of several epithelial organs.