Background & Aims: The role of the transferrin receptor and ferritin in the regulation of intestinal dietary iron uptake and excretion is unknown. This study aimed to determine the regulation of transferrin receptor and ferritin messenger RNA (mRNA) in the rat gastrointestinal tract in response to dietary iron changes. Methods: In situ hybridization studies for transferrin receptor and L-ferritin mRNAs were performed using tissues from normal, iron-deficient, and iron-loaded rats. Results: L-Ferritin mRNA was localized to small intestinal crypt and villus epithelial cells and colonic crypt and surface epithelial cells with mRNA levels up-regulated in iron-loaded rats. Transferrin receptor mRNA was detected in crypt epithelial cells of the small and large intestine in iron-deficient and normal vats. In contrast, in iron-loaded rats, transferrin receptor mRNA was also detected in the superficial epithelial cells of the small intestine and colon, which contained increased stores of iron. Transferrin receptor mRNA levels were increased in the colon. Conclusions: In the iron-deficient and normal rat intestine, transferrin receptor mRNA was expressed only by proliferating crypt epithelial cells. In iron-loaded rats, however, surface enterocytes of the intestine expressed both transferrin receptor mRNA and increased ferritin mRNA levels.