As they simulate the multilayer tissue architecture present in vivo, three-dimensional (3D) cultures of skin epithelial cells represent an attractive alternative for in vitro irritancy testing. In this study histology of non-commercial (Skin recombinant on de-epidermized dermis) and commercial models (Episkin, ZK 1300, Living Skin Equivalent) was compared. All 3D models possess a stratified epidermis with a differentiated stratum corneum. Their barrier function has been demonstrated by comparison of surfactants cytotoxicity on the 3D models and on human keratinocyte monolayer culture, and by the evaluation of the tritiated water penetration. All the 3D models showed permeability higher than fresh skin, the skin recombinant on DDED being the less permeable. However, reconstituted skin models possess several advantages for dermotoxicity testing, including the standardized nature of the epithelia and their suitability for testing water-insoluble compounds.