Purpose: This study was designed to determine if luminally administered glutamine alone functions as a growth factor or is synergistic with hepatocyte growth factor (HGF) after massive small bowel resection (MSBR). Methods: Twenty Sprague-Dawley rats underwent an 80% small bowel resection and jejunostomy tube placement. Seven days later the rats were divided into four groups: group 1, control, no further treatment (n = 5); group 2 received glutamine (4% of total food intake per day) via an orogastric tube (n = 5); group 3 received intraluminal HGF via a jejunostomy tube at 75 mu g/kg/d (n = 5); and group 4 received glutamine and HGF at the same doses, respectively. After a 14-day HGF infusion, glutamine feeding, or both combined, [C-14] glycine absorption (mu mol/L/cm(2) intestine) and mucosal DNA and protein content (mu g/mg mucosa) were measured in the remaining small bowel. Results: Glutamine alone had no effect on substrate absorption and protein or DNA content. HGF increased galactose absorption (106% increase over control, P < .01), glycine absorption (95% increase over control, P < .05), protein content (44% increase over control, P < .01), and DNA content (32% increase over control, P < .01). The combination of glutamine and HGF did not prove to be synergistic. Conclusions: These data demonstrate that in this short bowel model, glutamine alone did not enhance intestinal function. Furthermore, glutamine is not synergistic with HGF. This study suggests that glutamine alone may not be useful clinically in patients with inadequate intestinal function. Copyright (C) 1998 by W.B. Saunders Company.