Massive small bowel resection with re-anastomosis of the residual jejunum and terminal ileum results in marked adaptive responses. Various luminal and humoral factors have been implicated in the adaptive response, which may be analogous to the changes occurring in the ileum in the postnatal growth phase. Enteroglucagon, which is synthesized in the L cells of the intestinal mucosa, is thought to be an important humoral factor in this response. In this study, the levels of glucagon gene expression in the rat ileum both after massive small bowel resection and during development are examined. Glucagon messenger RNA levels are increased threefold as part of the adaptive response; the increase is maximal at 2 days and is at least partly dependent on luminal nutrition. Levels of glucagon messenger RNA in the developing ileum increase in the postnatal period until weaning when they decrease somewhat before gradually reaching adult levels.