Structure and function of skin are dependent upon interaction of the cells and matrix components that are unique to skin which, in turn, are dependent upon an interactive message system of cytokines acting over distance. Our laboratory has utilized a system which is sufficiently complex to permit a component of the skin to mature into a functional unit that can be indirectly influenced by cell types inherent to the skin, message over distance. The system, human epidermal cells, maturing into an epidermis on an overlying Millicell-HA membrane in the presence of normal fibroblasts or peripheral blood mononuclear cells in a lower chamber has been used to assess the role of interactive cytokines in skin. Data demonstrate: (a) normal fibroblasts enhance the outgrowth and induce a more organized phenotype in squamous cell carcinoma cells; (b) keratinocytes enhance fibroblast proliferation while squamous cell carcinoma cells suppress fibroblast proliferation, and (c) both activated and nonactivated mononuclear cells affect the outgrowth and organization of the squamous cell carcinoma cell line. It is concluded that cells of the skin, by their mediators, do affect the growth of one another in a highly interactive way.