Ultraviolet B (UVB) radiation in the skin induces pigmentation that protects cells from further UVB damage and reduces photocarcinogenesis. Although the mechanisms are not well understood, our laboratory has shown that UVB radiation causes increased MSH receptor activity by redistributing MSH receptors from internal pools to the external surface, with a resultant increase in cellular responsiveness to MSH. By this means, UVB and MSH act synergistically to increase melanin content in the skin of mice and guinea pigs. In humans, MSH causes increased skin pigmentation, predominantly in sun exposed areas. We have shown recently that UVB irradiation and exposure to MSH or to dbcAMP, stimulates production of mRNAs for both αMSH receptors and POMC in human melanocytes and keratinocytes. This indicates that at least one action of UVB on the pigmentary system is mediated through increased MSH receptor production, as well as through the production of the signal peptides, MSH and ACTH, that can further activate MSH receptors. The results add support to the hypothesis that the effects of UVB on cutaneous melanogenesis are mediated through a series of coordinated events in which MSH receptors and POMC-derived peptides play a central role.