The skin as an organ contains a large pool of cells, important for the production of various cytokines. This study focuses on interferon-beta (IFN-beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) production by fibroblasts and epithelial cells in response to interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). Both these primary cytokines show multiple biologic activities in the skin. Their antiviral activity on fibroblasts is mediated by IFN-beta and not by IL-6. In addition, TNF-alpha and IL-1 have a growth stimulatory effect on dermal fibroblasts, which is not mediated by IFN-beta or IL-6. IL-1, double-stranded RNA, or virus are potent inducers of IL-6 and IL-8 on dermal fibroblasts, but they are less efficient on epidermal cells. IL-8 has been discovered as an early acting skin reactive factor responsible for the chemotaxis of neutrophilic granulocytes. Furthermore, IL-1 possesses delayed skin reactivity upon intradermal injection which presumably is mediated by local release of IL-8. These findings demonstrate that cytokines also interact in the skin and that dermal fibroblasts play an important role in the regulation of aspecific host defense.