Disaggregated epidermal cells, sheets of epidermis, and explants of partial and full-thickness skin have been grown in cell, organ, and explant cultures. Each type of epidermal sample has also been "cultured" as a graft on a living animal host. The extent of tissue-specific phenotypic expression by the epidermal cell varies with the type of culture and the culture conditions: medium, biologic and pharmacologic additives, substrate, cell density, pH, and temperature. Specific culture conditions can be chosen to select for certain phenotypic traits. In spite of the diversity of conditions that may be used for culture, keratinocytes in cell, explant, and organ cultures undergo a similar pattern of differentiation. They stratify and keratinize, but rarely express a complete program of keratinization. Many of the characteristics associated with this pattern of differentiation are also observed in fetal epidermis during development. In culture, normal tissue architecture is usually absent; cells organize in flattened, loosely associated layers, synthesize a different pattern of keratin polypeptides, form keratohyalin granules only sporadically, and rarely contain lamellar granules. Epidermal differentiation in explant and organ cultures can be evaluated in regions of the explant, epibolic zone, and outgrowth apron. The epidermis of the original explant undergoes hyperproliferation, degeneration, sloughing, and then regeneration of a thin tissue. The cells in the epithelial outgrowth zone stratify and differentiate almost identically with those in cell culture. Neogenesis of structures in the basement-membrane zone can be followed in all three regions of the explant culture. Sheets of epidermis or epidermal cells transplanted onto or into a host animal show the most complete expression of the epidermal phenotype. After a period of hyperplastic growth, the cell layers become established in a pattern nearly identical to that in vivo. A complete granular layer is formed and stratum corneum cells, which are structurally and biochemically equivalent to those in tissue, differentiate. In some instances, the epidermis reconstructed from cells or tissue is indistinguishable from adjacent host epidermis. Experiments that include serial transfer from one culture system to another demonstrate the plasticity of the epidermal cell and its ability to respond variously to its environment.