The transcription factor NF-κB plays a critical role in immune and inflammatory responses. Here we show that poly (ADP ribose) polymerase (PARP) is required for specific NF-κB transcriptional activation in vivo. The activation of the HIV-LTR promoter and an NF-κBdependent artificial promoter was drastically reduced in PARP (_/_) cells, independently of the signaling pathway through which NF-bB was induced. Furthermore NF-κB-dependent gene activation was restored in vivo by the expression of PARP in PARP (_/_) cells. Finally, we show that both NF-κB and PARP formed a stable immunoprecipitable nuclear complex. This interaction did not need DNA binding. Our results suggest that PARP is an important cofactor in the activation cascade of NF-κB-dependent target genes.