Abstract To improve intestinal function in children with short bowel syndrome, our labortory has focused on identifying substances, which may enhance the function of small intestine epithelium. Previous studies have demonstrated that gastrin appeared to exert a trophic effect on the gastrointestinal tract. We chose to evaluate the influence of chronic, systemic, and luminal administration of gastrin-17 on substrate absorption in both fetal and mature rat small intestine. Transplanted fetal small intestine, mature small intestine in situ, and isolated mature small intestine segments were the surgical preparations used. Saline (control) or gastrin-17 (13.5 nmol/kg/d) was adaministered continuously for 14 days either systemically or luminally using osmotic pumps. The response to the saline or gastrin-17 infusions was determined by measuring absorption of radiolabeled substrates (14-C-galactose and 14-C-glycine). Following transplantation of fetal small intestine to a syngeneic host, galactose absorption rose 250% ( P < .01) and glycine absorption rose 130% ( P < .05) when compared with controls (N = 10). The response of mature jejunum and ileum following systemic gastrin infusion was a mild to moderate rise in galactose and glycine absorption, although statistical significance was not achieved. However, following luminal gastrin infusion into mature small intestine segments, there was a 4.54 fold rise in galactose absorption ( P < .01) and a 4.79 fold rise in glycine absorption ( P < .01) when compared with controls. These data suggest that gastrin can enhance substrate absorption in rat fetal and mature small intestine and that luminal perfusion appears to induce the greatest response. Further investigation is warranted to determine if gastrin can be a potential clinical tool in the treatment of short bowel syndrome.