IL-1 alpha and IL-6 are important pro-inflammatory and immunomodulatory cytokines and their production by oral (OK) and skin keratinocytes (SK) was compared. OK and SK produced IL-1 alpha, but not IL-6, constitutively. TNF alpha stimulation increased IL-1 alpha production by both cell types and exhibited synergy with interferon gamma (IFN gamma), although the latter had no effect by itself. In contrast, both cell types produced IL-6 in response to TNF alpha, IFN gamma or IL-4. and IFN gamma and IL-4 exhibited synergy with TNF alpha. For all cytokines the levels of IL-6 production were greater for OK than SK and OK, but not SK, produced IL-6 in response to IL-1 alpha stimulation. In addition, the IL-6 response to IL-4 stimulation was more rapid for OK than SK. These observations may explain the similarities and differences in wound healing and immuno-inflammatory diseases affecting the Skin and oral mucosa.