Integrin receptors containing an α4 subunit mediate cell-cell adhesion by binding to VCAM and MadCAM-1 in addition to supporting cell-extracellular matrix (ECM) adhesion by binding to the alternatively spliced V-region of fibronectin (FN). Studies in chick and mouse embryos have implicated these integrins in neural crest migration, myotube formation, heart development, and placentation. Because integrin-FN adhesive interactions have been shown to play essential roles in mammalian development, studies were initiated of integrin α4 in amphibian embryos, which are better suited to experimental analyses of the earliest stages of embryogenesis. Here, the cDNA cloning and pattern of expression of the Xenopus laevis homolog of integrin α4 is reported. Xenopus α4 is 55% identical at the amino-acid level to both its human and mouse counterparts, including conservation of an α4-specific protease cleavage site, 11 potential N-linked glycosylation sites, and 24 cysteine residues. in situ hybridization analysis reveals that transcripts encoding α4 are expressed in epidermis and the branchial arches. Although α4 transcripts can be detected as early as gastrulation, the protein is observed only after tailbud stages of development and is spatially restricted to the epidermis and gills of tadpole stage embryos. From these data it is concluded that Xenopus integrin α4 has structural features in common with other vertebrate α4 homologs, but is detected in a more restricted tissue distribution during development than α4 in other species.