Employing two types of brain ischemic animal models, an attempt was made to evaluate the protective effect of naftidrofuryl as the normalizing effect on the ischemia-induced changes in the brain levels of monoamines and metabolites. 1) During 2 min ligation of both left and right common carotid arteries of mice, dopamine (DA) content alone significantly decreased among three monoamines and four metabolites measured by a high performance liquid chromatography-electrochemical detection method. Pretreatment with naftidrofuryl oxalate (45 mg/kg, i.p.) was found to prevent the DA change, but the lower dose (15 mg/kg, i.p.) of the drug or any other drug tested individually (vinpocetine hydrochloride : 2 mg/kg, Ca hopantenate : 0.1 g/kg, citicoline : 0.1 g/kg, i.p.) had no such effect. 2) Infusion of carbon microsphere (500 particles/100 μl of 20% dextran/1.5 min/rat) into the right internal carotid artery induced various degree of time-dependent changes in the behavior and also in the brain levels of monoamines and metabolites. Embolized rats which otherwise would survive for at least 6 d after infusion, were divided into the lightly-infarcted and severely-infarcted groups by grading the behavioral abnormality. Subsequent treatments with naftidrofuryl oxalate (15 mg/kg, i.p., twice daily, totally 4 times) which was begun 16 h after microsphere injection, was found to accelerate the recovery rate of brain dopamine level once decreased by the embolism though only in the lightly-infarcted group. The significance of the results obtained herein were discussed in relation to the clinical effectiveness of naftidrofuryl in human brain ischemic diseases.