Normal human keratinocytes (HKC) are able to synthesize alpha-MSH. Because the production of alpha-MSH by HKC is induced significantly by ultraviolet B radiation, the involvement of keratinocyte-derived alpha-MSH in UV-induced immunosuppression has been suggested. The induction of the antiinflammatory cytokine IL-10 in monocytes is a major mechanism in the antiinflammatory actions of alpha-MSH. In the present study, HKC were investigated for their ability to produce IL-10 after alpha-MSH stimulation. HKC were obtained from the skin of human female breast sections and either left untreated or treated with 0.01 or 0.1 microg/ml alpha-MSH for different times. Using RT-PCR, HKC were shown to express IL-10 mRNA even under basal conditions, and treatment with alpha-MSH increased expression. Only minimal concentrations of IL-10 protein were detected in supernatants from the alpha-MSH-stimulated cultures. To the best of our knowledge this is the first report of IL-10 expression by cultured HKC after alpha-MSH stimulation. Further studies are needed to determine the biological and therapeutic relevance of these findings.