Melanocyte-stimulating hormone (MSH) receptor binding activity and melanocortin-1 receptor (MC1-R) gene expression on normal human melanocytes have been studied as responses to the effects of ultraviolet B (UVB), interleukin-1 (IL-1), endothelin-1 (ET-1) and tumour necrosis factor-alpha (TNF-alpha), which are known as UV sensitive regulators of melanocytic function. MSH receptor (MSH-R) binding activity was upregulated by UVB, IL-1alpha, -1beta and ET-1, but was downregulated by TNF-alpha. Northern blot analysis showed that MC1-R mRNA expression was induced 24 h after UVB irradiation in a dose-dependent manner, and that 24-h treatment with ET-1 also induced an expression of MC1-R mRNA, whereas TNF-alpha downregulated the expression. In addition, IL-1alpha and -1beta have a small but real inductive effect on MC1-R mRNA expression. Taken together, our results suggest a model in which higher MC1-R mRNA expression is accompanied by upregulation of MSH-R binding activity, and enhanced by UVB or cytokines sensitive to UVB. Such a regulatory system would enable normal human melanocytes to respond to MSH more efficiently and induce an increase of melanization of the skin through the MSH/MSH-R system after UVB radiation.