To assess potential mediators of adaptive bowel growth, ileal proglucagon messenger RNA (mRNA) ornithine decarboxylase (ODC) mRNA, plasma enteroglucagons, and plasma glucagonlike peptide I (GLP-I) were analyzed in rats soon after jejunoileal resection or control transection. Analyses were performed before and after refeeding to establish whether responses are nutrient dependent. The elevation of ileal proglucagon and ODC mRNAs within 12 hours after resection and before refeeding shows a nutrient-independent component of the adaptive response. The onset of adaptive growth of the ileum required luminal nutrient but occurred very rapidly, within 4 hours of refeeding. The onset of adaptive growth was accompanied by transient elevation of ileal ODC mRNAs. Ileal proglucagon mRNA and plasma GLP-I levels were also elevated, and these increases were sustained up to 8 days after resection. These early and sustained increases in proglucagon mRNA and plasma GLP-I indicate that in addition to the enteroglucagons, other intestinal proglucagon-derived peptides must be considered as potential mediators of adaptive growth after jejunoileal resection.