Popeye genes code for putative transmembrane proteins that are predominantly expressed in heart and skeletal muscle. Here we report on the isolation and expression of a previously unknown Xenopus member of this family, Xenopus Popeye-1 (Xpop-1). Xpop-1 is 60–65% identical to other vertebrate Pop-1 genes at the protein level. Whole-mount in situ hybridization studies revealed a highly specific expression of Xpop-1 whose transcripts are restricted to the embryonic heart and become enriched in the forming ventricle. Interestingly, unlike other known vertebrate Popeye genes, Xpop-1 is exclusively expressed in cardiac tissue and absent from skeletal muscle.