Members of the nuclear factor kappa-B (NF-kappa B) family of transcription factors are activated by tissue damaging stimuli that cause oxidative stress. The regulation of NF-kappa B activity in rat dorsal root ganglia (DRG) and the neural-crest derived pheochromocytoma cell line PC12 was examined. Electrophoretic mobility shift assays show that specific kappa B binding activities are present in DRG extracts and PC12 cells. These activities can be supershifted with antisera directed against p50, p52 and p65. South-western blots show the presence of a single NF-kappa B binding protein with picomolar affinity, co-migrating with NF-kappa B2 (p49/p52) immunoreactive material in dorsal root ganglia. Intraplantar injection of tumour necrosis factor but not nerve growth factor (NGF) induces NF-kappa B activity in the DRG of adult rats 6 h later. NGF has no effect on NF-kappa B activity in PC12 cells after 6 h, but elevates NF-kappa B activity more than 5-fold after 24 h treatment. These data suggest a role for NF-kappa B in delayed rather than immediate-early responses of the peripheral nervous system and related cell lines to inflammatory cytokines.