Hepatocyte growth factor in human placenta and trophoblastic disease. The hepatocyte growth factor (HGF) is an acidic protein with a strong mitogenic effect on hepatocytes. Hepatocyte growth factor mRNA recently was cloned from a placental cDNA library. Here we demonstrate the purification of HGF from human placenta with heparin-agarose chromatography and TSK-heparin high-pressure liquid chromatography and describe the distribution of placental HGF by immunohistochemistry using a polyclonal antibody to HGF. The yield of HGF from the placenta was approximately 100 to 200 times greater than that previously obtained from human plasma. Placental HGF was expressed strongly in the villous syncytium, extravillous trophoblast, and amnionic epithelium, and, to a lesser degree in endothelial cells and villous mesenchyme. Hepatocyte growth factor also was identified in the trophoblast of complete hydatidiform moles, choriocarcinomas, and a case of blighted ovum. The presence of HGF in an organ characterized by rapid cell proliferation during gestation and in trophoblastic tumors strongly suggests that the growth-regulating effect of HGF is not limited to hepatocytes. 