The cerebral protective action of nizofenone was compared with that of pentobarbital (PBT) in Mongolian gerbils in which an incomplete circle of Willis causes the development of ischemic damage in the cerebral hemispheres following common carotid arteries occlusion. The mean survival time following occlusion of both common carotid arteries which induced a mortality rate of 100% was 2.3 hr for the control group and 3.3 hr (P less than 0.05) and 4.1 hr (P less than 0.01) for the animals pretreated with nizofenone (10 mg/kg) and PBT (60 mg/kg), respectively. The mortality rate during a 1 month period following transient bilateral occlusion of the carotid arteries for 30 min was 100% for the control group and 41% (P less than 0.01) and 40% (P less than 0.01) for the animals pretreated with nizofenone (30 mg/kg) and PBT (60 mg/kg), respectively. No significant protective action was observed when administration of the drugs was carried out immediately after the onset of recirculation. These results suggest that nizofenone may be an effective cerebral protective agent.