Previous reports have demonstrated an increase in nuclear factor-kappa B (NF-kappa B) activity in response to UV radiation. These studies have essentially focused on the DNA-damaging fraction of solar UV radiation (UV-B and UV-C). In contrast, the effects of UVA radiation (320-400 nm) on NF-kappa B are not well known. In this study, we present evidence that UV-A radiation induces a marked decrease in NF-kappa B DNA-binding activity in NCTC 2544 human keratinocytes. In addition, NCTC 2544 keratinocytes pretreated with UV-A fail to respond to NF-kappa B inducers. Moreover, UV-A radiation induces a decrease in NF-kappa B-driven luciferase reporter gene expression in NCTC 2544 keratinocytes. The expression of the gene encoding I kappa B alpha (I kappa B is the NF-kappa B inhibitor), which is closely associated with NF-KB activity, is also reduced (3-fold) upon UV-A treatment. Our results indicate that the UV-A-induced decrease in NF-kappa B DNA-binding activity is associated with a decrease in the levels of the p50 and p65 protein subunits. This is the first evidence that an oxidative stress, such as UV-A radiation, may induce a specific decrease in NF-kappa B activity in mammalian cells, probably through degradation of NF-kappa B protein subunits. These findings suggest that UV-A could modulate the NF-kappa B-dependent gene expression.