The extracellular matrix glycoprotein tenascin is sparsely distributed in normal human dermis. The authors have shown that in a number of skin diseases (psoriasis, skin tumors), tenascin expression is strongly increased. In this immunohistochemical study, using polyclonal and monoclonal antisera, we have tested the hypothesis that tenascin expression in vivo is linked to epidermal proliferation. Using the sellotape stripping model in normal human skin, which causes a rapid recruitment of keratinocytes into the cell cycle, induction of tenascin expression was found in the upper dermis within 24 hours after stripping. In contrast, in normoproliferative monogenic disorders of keratinization (X-linked recessive ichthyosis, autosomal dominant ichthyosis vulgaris, non-erythrodermic lamellar ichthyosis), no increase in tenascin expression was found compared with normal skin. These findings demonstrate a relationship between epidermal proliferation and metabolic alterations in the dermal compartment.