Mouse cDNA clones coding for a desmocollin and a desmoglein, desmosomal cadherins that are putative adhesion molecules of the desmosome type of cell-cell junction characteristically found in epithelial tissues, have been isolated and sequenced. From sequence comparisons with the known human and bovine desmosomal cadherins, these clones represent a mouse Dsc3 and Dsg1. By interspecific backcross analysis, these genes were found to be closely linked in the proximal region of mouse chromosome 18, a region having conserved synteny with human chromosome 18. From these results, and recently reported linkage of DSG1 and DSG2 on human chromosome 18 at 18q12.1 in a deletion panel of somatic cell hybrids, all the desmosomal cadherins genes so far examined are clustered on chromosome 18 in human and mouse, which may have implications for gene expression. We further show that the human DSC3 gene, previously reported to be located on chromosome 9, also maps to human chromosome 18.