Our previous study demonstrated that the inhibition of interleukin-1β (IL-1β) reduces ischemic brain injury; how-ever, the molecular mechaism of the action of IL-1 in cerebralischemia is unclear. We are investigating cur-rently the role of NFkB during focal cerebral ischemia, usingmutant mice deficient in the interleukin-1 convert-ing enzyme gene (ICE KO) in a middle cerebral artery ocfclusion (MCAO) model. Adult male ICE KO and wild-type mice (n=120) undervent up to 24 hu of permanent MCAO. Cytoplasmic phospho-NFkB/p65 expression in ischemic brain was examined using Western Blot analy-sis and immunohistochemistry. NFkb DNA-binding ac-tivity was detected using electrophoretic mobility shift assay (EMSA). furthermore, ICAM-1 expression was ex-amined in both the ICE KO and wild-type mice (WT). Western blot analysis and immunostaining showed that the level of cytosolic phosphorylated NFkB/p65 in-creased after 2 and 4 hr of MCAO in WT mice; however, NFkB/p65 was significantly reduced after MCAO in the ICE KO mice (p<0.05). EMSA showed that NFkB DNA-binding activity increased after MCAO in WT mice;but this effect was reduced in the ICE KO mice. The number of ICAM-1-positive cessels in the ischemic hemiwphere was greatly attenuated in the ICE KO mice (p<0.05). which paralleled the results of immunohistochemistry. Our results demonstrate that NFkB phosphorylation is reduced in ICE KO mice, suggesting that ICE or IL-1 are involved in early NFkB phosphorylation. Because cere-bral ischemia induced infarction is significantly reduced in ICE KO mice, we conclude that early NFkB phosphorylation plays a disruptive role in the ischemic process.