Hepatocyte growth factor (HGF) stimulates the growth of hepatocytes and other epithelial cells. A gene for the HGF receptor, c-met, is detected in the intestinal tract and the liver, as well as in gastric carcinoma cells. However, the role of HGF in the regeneration of the normal gastric mucosa is not known. The purpose of the present study was to elucidate the effects of HGF on the morphogenesis of cultured gastric mucosal cells and to evaluate the role of HGF and c-met in the healing process in rat gastric mucosa. The cultured gastric mucosal cells developed a branching morphology in a collagen matrix supplemented with HGF or fetal calf serum. They did not form this morphology on a plastic dish or in the collagen without HGF or the serum. In an in vivo study, total RNA was extracted from rat gastric mucosa 6, 24, 48, and 96 hr after the exposure to a solution of 0.6 M HCl. HGF messenger RNA was not detected, but c-met was expressed in the mucosa. The increased expression of c-met was followed by healing of the mucosal injury. These results indicate that HGF plays important roles in the morphogenesis of gastric mucosal cells and that the HGF receptor gene participates in the healing process of gastric mucosa.