We have previously reported that the combined administration of mannitol and perfluorochemical blood substitutes is evidently effective in protecting the brain from cerebral ischemia. This experimental study was designed to develop more effective method in suppressing brain infarction than the combined treatment of mannitol and PFC. Using the "Canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump, the effect of eight agents including six kinds as the free radical scavenger on cerebral ischemia was investigated. Eight agents were mannitol, vitamin E (Vit. E), dimethyl sulfoxide (DMSO), vitamin C, glycerol, nizofenone (Y-9179), dexamethasone (Dexa.) and suloctidil (MY-103). After pretreatment with each agent, blood flow was reduced via the pump to 1/10 of the normal state and 1 hour later, return to the normal state was allowed. Subsequent changes in EEG were observed and the effects of the drugs evaluated. In the control group, no recovery of electrical activity was seen, but in six groups among eight treated groups, i.e., treated with mannitol, Vit. E, DMSO, MY-103, Y-9179 and Dexa, gradual emergence of slow waves was observed. And more favorable effects were found when the combined administration of mannitol, Vit. E and Dexa was made in the same experimental schedule as compared with the single administration of each of these drugs. Furthermore in the animals administered with PFC in combination with mannitol, Vit. E and Dexa, flattening of electrical activity could not be seen throughout the period of severe ischemia. Moreover, the power of electrical activity recovered nearly to the preischemic state immediately after recirculation. Although the possible mechanisms are not yet completely clarified, the present results are thought to indicate that this new combination therapy utilizing PFC with mannitol, Vit. E and Dexa may be useful in the treatment of cerebral ischemia.