The aim of the present study was to investigate the presence of stratum corneum chymotryptic enzyme (SCCE) in human epidermis reconstructed in vitro on dead de-epidermized dermis and the effect of retinoic acid (RA) on its expression. SCCE is a recently discovered serine proteinase which has been purified from human stratum corneum, and evidence has been presented that it may play a role in stratum corneum turnover, especially in desquamation. The SCCE-specific monoclonal antibody TE-9B showed positive immunofluorescence staining of high suprabasal keratinocytes, mainly in the stratum granulosum, in normal non-palmo-plantar human epidermis as well as in reconstructed epidermis in the absence of RA. This staining was also seen in reconstructed epidermis cultured in the presence of 10(-8) M RA, a concentration at which the reconstructed epidermis still formed an orthokeratotic stratum corneum. At 10(-7) M RA, however, not only the formation of the stratum corneum but also SCCE expression was suppressed. These results support the hypothesis that SCCE expression is related to and may be part of the epidermis-specific differentiation program, where the enzyme may be involved in the homeostasis of the stratum corneum, possibly by degrading the intercorneocyte cohesive structures.