After 30 s ischemia induced by decapitation, the contents of ATP and phosphocreatine (PC) in mouse brain reduced, while that of lactic acid (LA) increased. When mexiletine (3.1-50 mg.kg-1) was injected ip 30 min before decapitation, the brain ATP and PC reduction, and LA accumulation were both alleviated in a dose-dependent manner. These findings suggested that mexiletine was effective in ameliorating the energy exhaustion in the ischemic brain.