Hepatocyte growth factor (HGF), originally known to stimulate hepatocyte DNA synthesis, recently has been shown to enhance growth of intestinal epithelial cells in vitro. However, there have been no studies on the effect of HGF on the function of intestinal epithelial cells in vivo. This study was designed to examine the effect of systemically administrated HGF on intestinal epithelial cell mass and function. Twenty young adult male Sprague-Dawley rats underwent placement of jugular venous catheters connected to subcutaneously placed osmotic minipumps. The rats were divided into four groups based on the contents in the osmotic pump: Group 1 (control, n = 5), normal saline; Group 2 (n = 5), HGF 75 microg/kg/d; Group 3 (n = 5), HGF 150 microg/kg/d; and Group 4 (n = 5), HGF 300 microg/kg/d. After a 14 day infusion, [C14] galactose and [C14] glycine absorption were measured in a 10-cm segment of mid small intestine using an in vivo closed-recirculation technique. Mucosal DNA content and protein content of the same small bowel segment were determined for each group. With all three doses, HGF significantly increased DNA content (P < .01) and protein content (P < .05). HGF also significantly increased galactose absorption (P < .01) with all three doses. Glycine absorption was increased with a dose of 75 (P < .05) and 150 microg/kg/d (P < .01), but not at a dose of 300 microg/kg/d. These data demonstrate that HGF can increase intestinal epithelial cell mass and function in vivo. HGF may be clinically useful in patients with short bowel syndrome.