Human endometrial regeneration has been considered to be modulated by several growth factors. However, little is known about the detailed mechanisms involved in the repair of the endometrium during the menstrual period. Hepatocyte growth factor (HGF) is a pleiotropic growth factor that reportedly acts on various epithelial cells. In the present study, we observed HGF and mRNA expression in human endometrium and mRNA expression in cultured endometrial epithelial cells of the c-met gene by reverse transcription-polymerase chain reaction and Southern blot hybridization. We also examined the biological role of HGF on the regeneration of the endometrium by using cultured endometrial epithelial cells in their proliferative phase. With the proliferation assay, the addition of 10-50 ng/ml of HGF showed that HGF was mitogenic in a dose-dependent manner. With Boyden's chamber technique, 50 ng/ml of HGF significantly stimulated cell migration. In a three-dimensional cell-culture system, the endometrial epithelial cells formed cell clusters and gradually formed epithelial lumens, both of which were stimulated by 50 ng/ml of HGF. Results suggest the HGF stimulates the proliferation and migration of, and morphogenic changes in, endometrial epithelial cells. HGF may modulate the regeneration of the endometrium during menstruation.