Evidence suggests that inherent in skin of psoriatic subjects are cells, architectural structures, and/or mediators, which are, at a minimum, responsible for its hyperproliferative epidermis. An objective of our laboratory has been to establish an in vitro definition of this inherent aberration. Fibroblasts are important to epidermal proliferation/differentiation. This, and an unconfirmed report that fibroblasts from psoriatic subjects might drive the abnormal epidermal proliferation in psoriasis, have caused further focus on the fibroblast. Data show that fibroblasts from patients with psoriasis, both involved and uninvolved, in the presence of human serum, either normal or psoriatic, have an increased rate of proliferation. Fibroblasts from uninvolved psoriatic sites are most responsive. To determine if fibroblasts from psoriatics could induce the psoriasiform phenotype on normal keratinocytes, an interactive skin equivalent system has been developed. With this system, fibroblasts from uninvolved and involved sites cause normal keratinocytes to have an enhanced outgrowth. Uninvolved fibroblasts cause the greatest changes. The nature of the skin equivalent system calls for this to occur via message over distance. We conclude that fibroblasts from psoriatic subjects can induce a psoriasiform phenotype via a soluble message.