Adhesional glycoproteins of desmosomes possess asparagine-linked, complex oligosaccharide side chains. We investigated the potential of these sugars to protect the core proteins of desmosomes and corneosomes (modified stratum corneum desmosomes) against proteolysis. Isolated pig ear epidermis was exposed sequentially to individual hydrolases, and their effect monitored ultrastructurally. Two major steps were employed: (1) glycosidases, to remove stepwise the sugars in a typical complex oligosaccharide chain; and (2) proteolysis using both endopeptidases and an exopeptidase. Controls were exposed to the same sequence of buffers, but without enzymes. Proteases alone induced no major changes in desmosomes or corneosomes compared with controls. Glycosidases alone, or proteases followed by glycosidases, caused mild fragmentation of the desmosomal interspace, but no widening. However, dramatic changes occurred when glycosidase treatment was followed by proteolysis. The interspace of both desmosomes and corneosomes was extensively digested, and consequently widened, causing loose packing of the epidermis. These findings indicate that sugars are potentially anti-proteolytic in both desmosomes and corneosomes. Sugars may, therefore, be a factor in presenting premature desquamation, by protecting desmosomes and corneosomes against extracellular proteases derived from membrane-coating granules.