The amphibian intestine has two morphologically distinct structures during development. Early embryogenesis generates a simple, tube-like intestine in the tadpole whereas after thyroid hormone (T 3 )-dependent metamorphosis a newly remodeled adult intestine is formed similar to that of higher vertebrates. This change requires a drastic transformation of the epithelial layer. We have isolated a Na 1 /PO 4 32 cotransporter gene that may contribute to this transformation. The deduced amino acid sequence of this gene shows a high degree of homology to the mammalian renal Na 1 /PO 4 32 cotransporters, which have little or no expression in organs other than the kidney. The frog gene is highly expressed and regulated by T 3 in the intestine with little expression and/or regulation by T 3 in most other organs. Its mRNA is restricted to the differentiated epithelial cells both in tadpoles and postmetamorphic frogs. Interestingly, its expression is low in premetamorphic tadpoles, but up-regulated when metamorphosis is initiated by endogenous T 3 . As the larval epithelium undergoes programmed cell death (apoptosis), the mRNA level drops to a minimum. Subsequently, the gene is reactivated at the tip region of the newly formed adult intestinal folds and a crest-trough polarity of expression is established by the end of metamorphosis. This temporal regulation profile is also reproduced when premetamorphic tadpoles are treated with T 3 to induce precocious intestinal remodeling. These results suggest a possible role of the Na 1 /PO 4 32 cotransporter during metamorphosis and demonstrate that the adult epithelial cell differentiation pattern is established in the direction of crest-to-trough of the intestinal fold, concurrent with the epithelial morphogenic process.