The cerebral protective effect of nizofenone against tissue oxygen deficiency was investigated in mice. Treating mice with nizofenone resulted in a dose-dependent decrease in the rate of KCN-induced mortality and significant protection was observed at a dose as low as 0.3 mg/kg (i.p.). The cerebroprotective action of nizofenone was also demonstrated biochemically: Nizofenone (10 mg/kg i.p.) ameliorated KCN-induced anoxic disorder of cerebral energy metabolism, characterized by irreversible depletions of cerebral high energy phosphate stores and glucose concentrations and a marked accumulation of lactate, while keeping the cerebral energy charge potential (ECP) close to its normal value. Nizofenone showed similar effects in another experiment in which cerebral metabolic disorder was induced by complete ischemia following decapitation. These findings suggest that nizofenone has a considerable cerebroprotective action against oxygen deficiency.