This study investigated nuclear factor-kappa B (NF-kappa B) activity by electrophoresis mobility gel shift assay and I kappa B alpha expression by Western blot analysis in monocytes obtained from serial samples of internal jugular venous blood taken from seven migraine patients without aura during attacks. Inducible nitric oxide synthase (iNOS) expression was also assessed by reverse transcription-polymerase chain reaction. An increase in NF-kappa B activity peaked 2 h after attack onset. This was accompanied by a transient reduction in I kappa B alpha expression. Up-regulation of iNOS was evident at 4 h, maintained at 6 h and reduced at the end of the attack. These findings substantiate the hypothesis of transitory delayed inflammation, as suggested by the animal model, and suggest the possibility of using therapeutic approaches to target NF-kappa B transcription in the treatment of migraine.