Tenascin, a large glycoprotein of the extracellular matrix, shows a site-restricted distribution during embryogenesis, and can be found in adults in a variety of pathological conditions. In normal skin, tenascin is expressed at low levels, but it is upregulated in skin tumours, in a number of skin diseases with epidermal hyperproliferation and during wound healing. Several tenascin variants have been described, and these arise by alternative splicing. Using a monoclonal antibody recognizing all tenascin variants, and polyclonal antibodies specific for the large tenascin variants, we have investigated tenascin expression in bullous diseases such as epidermolysis bullosa, pemphigus, bullous pemphigoid and pemphigoid gestationis. By immunohistochemistry, we have found increased tenascin staining in all patient skin samples, with a more pronounced tenascin expression in samples of autoimmune bullous diseases. The large tenascin variants seem to be major forms of tenascin occurring in healthy skin. In patients with blistering diseases, however, these large variants appear to represent a subpopulation of the induced tenascin accumulation. These findings suggest different functions for the tenascin variants in normal and diseased skin.