Insulin-like growth factor I (IGF-I) and insulin may be important regulators of intestinal growth. To investigate small intestinal IGF-I receptors (IGF-IR) and insulin receptors (IR) during intestinal cell atrophy and regeneration, we compared indexes of IGF-IR and IR expression in rat jejunum after 72 h of fasting and 24-72 h of enteral refeeding. Fasting induced intestinal atrophy, reduced plasma insulin and IGF-I concentrations, and markedly decreased jejunal IGF-I messenger RNA (mRNA) levels; these changes were reversed by refeeding. Fasting significantly increased jejunal specific insulin binding, IR content (to 230% of the fed control value), and the 9.6- and 7.4-kilobase IR mRNA transcript levels (to 202% and 218% of control values, respectively). These IR indexes rapidly decreased to control levels with refeeding. Levels of IGF-IR (by Scatchard analysis) and IGF-I-R mRNA were not significantly altered with fasting. The 11-kilobase IGF-IR mRNA transcript increased significantly during the first 24 h of refeeding (to 166% of the control value), and IGF-IR number rose 3-fold. We conclude that rat jejunal IR and IGF-IR are differentially regulated by nutrient availability. Up-regulation of jejunal IGF-I and IGF-IR expression during refeeding suggests a role for the IGF action pathway in gut trophic responses to enteral nutrients.