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Exudative epidermitis is an acute, often fatal skin disease in piglets caused by infection with Staphylococcus hyicus. Clinical and histopathological manifestations of exudative epidermitis are similar to those of a human blistering skin disease, staphylococcal scalded skin syndrome, in which cleavage of desmoglein (Dsg) 1 by exfoliative toxins produced by S. aureus results in blister formation in the upper part of the epidermis. The aim of this study was to determine whether the four types of exfoliative toxin produced by S. hyicus (ExhA, ExhB, ExhC and ExhD) are able to affect swine Dsg1. We first generated recombinant toxins of ExhA, ExhB, ExhC and ExhD by an E. coli expression system. To determine the pathogenic activity of these recombinant toxins, we injected them subcutaneously into 3- to 4-week-old piglets. After administration of all four recombinant toxins, local exfoliations developed at the inoculation sites of the piglets’ skin at 21–48 h postinjection. To further assess whether these Exhs affect swine Dsg1, we incubated cryosectioned pig skin with Exhs in vitro and subsequently stained Dsg1 and Dsg3 by immunofluorescence with human pemphigus foliaceus sera and anti-Dsg3 monoclonal antibody (5H10), respectively. The cell surface staining of Dsg1 was abolished by incubation with any of the four isoforms of Exh, whereas that of Dsg3 was not affected at all. These findings indicate that all four types of exfoliative toxin produced by S. hyicus (ExhA, ExhB, ExhC and ExhD) can cause skin exfoliation in pigs with exudative epidermitis, presumably by digestion of Dsg1. Funding: Ministry of Education, Culture, Sports, Science and Technology of Japan. [ABSTRACT FROM AUTHOR]