Nuclear factor-kappa B (NF-kappa B) is an oxidative stress responsive transcription factor known to be activated in response to transient middle cerebral artery intraluminal occlusion. Since oxidative stress activation may largely occur during reperfusion, the aim of this study was to determine if permanent middle cerebral artery intraluminal occlusion without reperfusion induces NF-kappa B activation and the relationship of NF-kappa B activation to HSP70 expression and neuronal cell death. Our results suggest that permanent intraluminal occlusion is sufficient to induce NF-kappa B activation 7 h after the onset of occlusion. Interestingly, this activation seems to occur specifically in dying neurons of the penumbra area devoid of any HSP70 neuronal immunoreactivity. These findings are consistent with the suggested protective role of HSP70 expression and suggest that NF-kappa B activation observed in the penumbra area has a role in neuronal cell death after permanent intraluminal cerebral ischemia.