Ultraviolet B (UVB) radiation is known to induce reactive oxygen species (ROS) in the skin. The skin, however, counteracts ROS by both constitutional and newly produced antioxidants. One such antioxidant, adult T cell leukemia-derived factor (ADF), a human homologue of thioredoxin (TRX), was shown to be efficiently produced in and released from cultured normal human keratinocytes after UVB irradiation by Northern and Western blot analyses and enzyme-linked immunoabsorbent assay (ELISA). Recombinant ADF (rADF) did not rescue UVB-induced melanocyte death, either when added pre- or post-UV irradiation. However, further addition of neutralizing antibody caused cell death of both keratinocytes and melanocytes. rADF was shown to induce higher expression in melanocortin-1 receptor (MC1-R) mRNA accompanied by increased binding activity using 125I labeled [Nle4, D-Phe7]-alpha-MSH in melanocytes, leading to the enhanced increment of DNA synthesis. Taken together, it was shown that released ADF from UVB-irradiated keratinocytes acts as a survival factor for both keratinocytes and melanocytes but does not rescue UV-induced melanocyte death. Further, it may work as one of the stimulatory factors for UVB-induced melanogenesis by upregulating MSH-R binding activity in combination with the enhanced DNA synthesis by alpha-MSH.