Numerous functional and structural effects of pharmacological dosages of glucagon on the small-intestinal mucosa have been demonstrated. In addition, clinical conditions associated with elevated concentrations of plasma glucagon may go along with alterations of the intestinal mucosa. The physiological and pathophysiological relevance of these findings, however, is questionable in view of the heterogeneity of the findings, of the complexity of the experimental systems used and of the methodological problems involved. With respect to possible trophic effects on the small-bowel mucosa enteroglucagon is of special importance. Numerous diseases in which increased intestinal mucosal growth has been shown are associated with elevated plasma concentrations of enteroglucagon. Our results concerning radiation damage, the time course of plasma enteroglucagon levels during antimitotic treatment, the small intestinal resection and the experimental blind loop syndrome are discussed. An outlook will be given as to the use of monoclonal antibodies in the development of glucagon as well as enteroglucagon deficiency states for the study of the physiological relevance of these two regulatory peptides.