After massive small bowel resection, the remnant intestine undergoes compensatory adaptation. We tested the hypothesis that glucagon-like peptide-2 (GLP-2) is an endogenous mediator of postresection intestinal adaptation. Rats were allocated to 1 of 4 groups: groups 1 and 2 rats underwent mid-small bowel transection and reanastomosis; groups 3 and 4 rats underwent 75% mid-small bowel resection and reanastomosis. Groups 2 and 4 rats were administered 1.8 mg of antirat GLP-2 antibody twice daily beginning immediately after the surgical procedure; groups 1 and 3 rats were administered rabbit serum (control). Ileal specimens were harvested on postoperative day 7. Ileal mucosa from group 3 animals displayed morphologic and proliferative indices of adaptation. Each of these indices of adaptation was inhibited by GLP-2 immunoneutralization (group 4). Morphologic and proliferative parameters in the ileum from animals that had undergone transection with reanastomosis were unaffected by GLP-2 immunoneutralization. These results suggest that GLP-2 is an endogenous mediator of postresection intestinal adaptation.