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The cellular response to DNA-damaging agents is partly mediated by DNA-binding transcription factors such as p53 and nuclear factor kappaB (NF-kappaB). Typically NF-kappaB activation is associated with resistance to apoptosis. Following stimulation with UV light however, NF-kappaB activation has been shown to be required for programmed cell death. To study this effect further and to determine the relationship between NF-kappaB and p53 function, we have examined the effect of UV light on U2OS cells. UV stimulation resulted in the activation of NF-kappaB DNA-binding and the induction of p53. Surprisingly, and in contrast with tumour necrosis factor alpha stimulation, this UV- induced NF-kappaB was transcriptionally inert. These observations suggest a model in which the NF-kappaB switch from an anti-apoptotic to a pro-apoptotic role within the cell results from modulation of its ability to stimulate gene expression, possibly as a result of the ability of p53 to sequester transcriptional co-activator proteins such as p300/CREB (cAMP-response-element-binding protein)-binding protein.