The desmocollins, together with the desmogleins, are members of the cadherin family and constitute the adhesive proteins of the desmosome type of cell-cell junction. Here we describe a study of the promoter of the human form of the DSC2 gene which is the equivalent of the first isoform expressed in the developing mouse embryo and that has the most widespread tissue distribution in epithelia and also in desmosome-bearing non-epithelial tissues. Analysis of the 5' upstream region by DNA sequencing and Southern blotting suggested that it contained a CpG island, and a major site of transcription initiation 201 bp upstream of the translation start site was found by RNase protection and primer extension. There were no obvious CCAAT or TATA boxes present. Analysis of 1.9 kb upstream of the translation start site revealed consensus binding sites for transcription factors including Ap-2 and Sp-1, and motifs common to the promoters of other epithelially expressed genes such as keratin 14 and the desmoglein genes DSG1 and DSG3. Deletion derivatives defined a promoter of 525 bp which was active in epithelial cells and in mouse blastocysts with an intact epithelium. This promoter showed reduced expression in non-epithelial cells.