Epidermal-dermal interactions are important determinants of embryonic development in skin. This review examines the role of such epidermal-dermal interactions in the conservation of epithelial specificity in adult skin. The basic epidermal keratinization program as defined as a proliferative basal cell population, orderly stratified cytodifferentiation of the cells and production of stratum corneum can be expressed by adult epidermis without the continued presence of a specific dermis. This is evidenced by the ability of epidermis to differentiate fully in association with nondermal connective tissues. Several other epithelia including cornea and esophagus express their specific differentiative characteristics without the continued presence of specific connective tissue. On the other hand, certain regional epithelial specificities in adult skin may be determined by the dermis. These regional epidermal specificities involve alterations in epidermal thickness, size of epidermal compartments including the stratum corneum, and the folding pattern at the epidermal-dermal interface. Possible mechanisms by which dermis could control these regional characteristics are discussed. Epidermal-dermal recombination techniques have been used to define the site of gene action in a variety of inherited skin abnormalities in animals. Similar studies are reported utilizing adult human skin in long-term cultivation on nude athymic mice. The abnormal gene in lamellar ichthyosis exerts its effect directly on the epidermis. Generalized exfoliative psoriasis was also studied by recombination techniques. Both epidermis and dermis were required for the maintenance of psoriatic morphology, suggesting a complex polygenic mechanism or one involving both genetic and environmental factors.