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We here report that preservation of the basic epithelial–mesenchymal interactions allows for highly complexex vivofunction of epidermal cells. The approach taken is based on the preparation of organ fragments that preserve the basic epithelial/mesenchymal interactions but also ensure appropriate diffusion of nutrients and gases to all cells. Human and mice keratinocytes in such organ fragments, remain viable, proliferate and express epidermal-specific gene products when cultured in serum-free medium without added growth factors, for several weeksin vitro. When implanted into syngeneic animals they remain viable, become vascularized and continue to function and transcribe tissue-specific gene products for several months. Such fragments allow primary cellsex vivoto preserve most of the functional attributes of thein vivosystem. Clearly, the effect of the extracellular matrix is critical in this system in order for the cells to proliferate and differentiateex vivo. We are not aware of any other system which allows for localized expression of epidermal-specific genesex vivofor significant periods in culture in defined serum-free medium. [ABSTRACT FROM AUTHOR]