Stratum corneum chymotryptic enzyme (SCCE) may function in the degradation of intercellular cohesive structures in the stratum corneum preceding desquamation. Previous results have suggested that SCCE may be specifically expressed in squamous epithelia undergoing terminal differentiation and keratinization. The aim of the present work was to further elucidate the association between SCCE expression and terminal differentiation in squamous epithelia. Using immunohistochemical methods, we have examined the expression of SCCE in two diseases of human oral mucosa, which produce a pathological keratinization of the epithelium at sites which are normally non-keratinized. Affinity-purified polyclonal rabbit antibodies raised against recombinant SCCE and monoclonal antibodies against the differentiation-specific keratins nos. 10 and 13 were used on formaldehyde-fixed and paraffin-embedded biopsies. Whereas there was essentially no expression of SCCE in normal, non-keratinized buccal mucosa, there was a strong expression in suprabasal cells in orthokeratotic and parakeratotic areas of the lesions of oral lichen planus (an inflammatory disease) and benign oral keratosis (a non-inflammatory disease). There was a close association between the expression of SCCE and keratin no. 10, i.e. a keratin which is specifically expressed in cornifying squamous epithelia. The results suggest that SCCE expression may be a true marker of terminal differentiation in squamous epithelia and give further evidence for a role of SCCE in the formation and/or turnover of the stratum corneum.