Various peptide growth factors have been found to regulate epithelial cell function within the mucosal epithelium of the gastrointestinal tract. In this study hepatocyte growth factor/scatter factor (HGF/SF) was found to stimulate intestinal epithelial cell proliferation: 2.5-fold in the non-transformed rat small intestinal epithelial cell line IEC-6 and 1.9-fold in the human colon cancer-derived HT-29 cell line. In addition, HGF/SF enhanced epithelial cell restitution, the initial step involved in gastrointestinal wound healing, in an in vitro model. Migration of IEC-6 in wounded monolayers was enhanced up to 7-fold. Enhancement of restitution by HGF could be completely abrogated by addition of immunoneutralizing anti-TGF beta 1, indicating that this process is mediated through a TGF beta-dependent pathway. These findings suggest that HGF exerts functional effects on intestinal epithelial cell populations and may play a role in the morphogenesis of the gastrointestinal tract and its remodeling following injury.