The small intestine of tadpoles is an organ that undergoes extensive changes during the process of morphogenesis. These changes include the transformation of the intestine from a single layer of larval epithelia with thin connective tissue to an extensively folded adult epithelia with a native connective tissue layer. To investigate the molecular events that lead to these dramatic morphological changes, a novel 5′-suppression subtraction hybridization method was developed. We succeeded in identifying 24 upregulated genes in the remodeling intestine, of which 22 genes were unique Xenopus homologues of genes previously identified in other organisms. The homologue genes included transcription factors, extracellular matrix proteins, immunosuppressant-binding proteins, enzymes, cell adhesion molecules, morphogenetic proteins, growth factors, member of the ubiquitin proteosome pathway, RNA-binding proteins, and signal-transduction proteins. This approach to study the molecular events of intestinal metamorphosis holds great potential for understanding this complex biological process.