The generation of the free radical reaction in the ischaemic and hypoxic brain has been demonstrated using the chemiluminescence and the ESR techniques. The effects of various drugs, thought to be free radical scavengers were then tested in the ischaemic brain of dogs. It was found that not only mannitol, but also vitamin E, dexamethasone and other drugs have significant cerebral protective effects--particularly when administered together. Moreover, remarkable improvements were found when these 3 drugs were administered with the artificial blood substitute, PFC, which is known to have a high oxygen-carrying capacity. Finally, using the chemiluminescence and the ESR method, we have demonstrated that mannitol, vitamin E and glucocorticoids act as free radical scavengers and particularly mannitol acts as a scavenger of the hydroxy radical.