Interesting, recent studies have suggested a possibility that transcriptional factor NF-kappaB may play a functional role in the survival of mouse osteoclasts. However, it has not been known whether NF-kappaB is involved in apoptosis of and bone resorption by mature osteoclasts. Thus, using NF-kappaB inhibitors, we examined the functional role of NF-kappaB in the induction of apoptosis in rabbit mature osteoclasts. PDTC, a potent inhibitor of NF-kappaB, stimulated markedly apoptosis of the osteoclasts and inhibited bone resorption by these cells. These effects also was observed when three other inhibitors of NF-kappaB were used. And a gel mobility shift assay showed that PDTC also inhibited NF-kappaB binding to its consensus sequence in the cells. These results suggest a regulatory role for NF-kappaB in apoptosis in and bone resorption by rabbit mature osteoclasts.