A mouse gene, Cdx-1, was isolated from an embryonic cDNA library using a Drosophila caudal gene probe. The deduced amino acid sequence of Cdx-1 contains conserved sequence domains along the entire gene, as well as a highly conserved caudal-type homeo box. A structural comparison suggests a common ancestral origin of mouse Cdx-1 and Drosophila caudal. The expression of Cdx-1 during embryogenesis was analyzed by Northern blotting and in situ hybridization. Cdx-1-specific transcripts are localized in the epithelial lining of the intestines beginning at 14 days' gestation. The expression of Cdx-1 in the intestine continues into adulthood, but cannot be detected in any other tissues. The Cdx-1 gene is the first homeo-box-containing gene expressed in cells derived from the embryonic endoderm.