Murine monoclonal antibodies (mAbs) which specifically react, in immunoblot and immunolocalization experiments, with the human desmosomal cadherins, desmocollins Dsc1 (mAb Dsc1-U100) and Dsc3 (mAb Dsc3-U114), have allowed to study systematically the synthesis of these proteins in tissues and cultured cells. Application of these mAbs in immunofluorescence microscopy on human skin has shown the presence of Dsc1 in the suprabasal layers of interfollicular epidermis and a specific cell layer of the hair follicle root sheath, whereas Dsc3 has been identified in all living epidermal layers as well as in glandular ducts and in basal matrix cells and the outer root sheath of hair follicles. Dsc3, but not Dsc1, it also present in desmosomes of the basal as well as suprabasal cell layers of other stratified epithelia such as vagina, tongue and esophagus as well as in cells of the basal layer of bladder urothelium and the complex epithelium of trachea. All the diverse one-layered ("simple") epithelia examined were as negative for both, Dsc1 and Dsc3, as were the non-epithelial desmosomes of the intercalated disks of the myocardium. A special situation has been discovered in the thymus. Here the usually single-layered cells of the thymic reticular epithelium are connected by Dsc3-possessing desmosomes, as they also contain typical (type I) hemidesmosomes, whereas Dsc1 is only detected in the "Hassall bodies", spheroidal formations of densely packed reticulum-derived cells which also produce cytokeratins 1 and 10, indicative of suprabasal epidermal differentiation. In cell cultures most, probably all, desmosomes of diverse cell lines derived from stratified squamous epithelia or squamous cell carcinomas, including primary keratinocytes, HaCaT keratinocytes and A-431 carcinoma cells, contain Dsc3. By contrast, Dsc1 has only been detected in local piles of keratinocytes that appear to be in the process of suprabasal differentiation. The antibodies have also allowed to demonstrate that desmosomes of cell lines can contain more than one desmocollin isoform. The observations made by immunofluorescence microscopy are compared with results obtained by in situ hybridization of mRNAs, and the potential value of these mAbs in histology and pathology is discussed.