Desmosomal cadherins, transmembrane glycoproteins of the cadherin family of cell adhesion molecules, comprise two subfamilies, the desmogleins and the desmocollins, each of which consist of at least 3 distinct proteins encoded by individual genes. We have analyzed the expression of desmogleins Dsg1 (Pemphigus foliaceus antigen), Dsg2 ("simple epithelium type") and Dsg3 (Pemphigus vulgaris antigen) in various normal tissues and diverse carcinomas, using RNase protection assays. We found that the gene encoding Dsg2 was expressed in most epithelial tissues and carcinomas whereas mRNAs encoding Dsg1 and Dsg3 were primarily restricted to stratified squamous epithelia and certain (mostly squamous cell) carcinomas. Antisera raised against recombinant polypeptides corresponding to various parts of Dsg2 produced immunostaining along intercellular borders of simple epithelia and basal cells of non-cornifying stratified squamous epithelia but were negative with most cells of epidermis. Preliminary analyses of carcinomas revealed comparable patterns. These cell type-specific differences in the molecular composition of desmosomes, which are also reflected in carcinomas, open new possibilities for the histological classification and subtyping of carcinomas. Moreover, the functional importance of desmosomal cadherins in the adhesion of carcinoma cells and during metastasis makes them a promising marker system for the assessment of the biological behaviour of carcinomas.