The Na(+)-independent Cl-/HCO3- exchangers in many tissues are encoded by AE2, which is a member of the anion-exchanger (AE) gene family. Molecular regulation of AE2 remains mostly unknown. In this study, AE2 mRNA levels during enterocyte differentiation and intestinal development were examined in rat small intestines. AE2 mRNA levels did not show obvious segmental variation or vary along the crypt-villus axis. In contrast, AE2 mRNA decreased between days 14 and 21 after birth, the period corresponding to the transition period between the suckling and weanling stages in rats. Effects of L-thyroxine and dexamethasone on AE2 expression were examined because these hormones play important roles in gene regulation during development. L-Thyroxine administration starting on day 9 after birth led to an approximately 60% decrease (P < 0.001) in AE2 mRNA on day 13. Dexamethasone had no effect on AE2 mRNA level regardless of whether the hormone was administered alone or in conjunction with L-thyroxine. Our results indicate that AE2 mRNA in the intestine is regulated during development and that this regulation may in part be related to hormonal changes.