1. The present study was designed to determine whether naftidrofuryl oxalate exerts a possible therapeutic effect on brain energy metabolism impaired by microsphere-induced cerebral embolism in vitro. 2. Injection of microspheres into the right carotid canal resulted in a decrease in tissue high-energy phosphates both in the right and left hemispheres, and an increase in tissue lactate in the right hemisphere, on the 3rd and the 5th day after the embolism. The embolism also induced a marked reduction in mitochondrial oxidative phosphorylation ability and succinate dehydrogenase activity. The results suggest that severe ischaemia was induced in the brain by the microsphere administration. 3. Treatment of microsphere-injected rats with naftidrofuryl oxalate (15 mg kg-1) for 3 or 5 days elicited a significant recovery of tissue high-energy phosphate and lactate levels. The recovery was associated with a significant restoration of mitochondrial succinate dehydrogenase activity on the both days and of mitochondrial oxidative phosphorylation rate on the 5th day. 4. The results suggest that naftidrofuryl oxalate is beneficial in the recovery of cerebral energy metabolism impaired by microsphere-induced cerebral ischaemia, presumably through a mechanism involving its direct effect on the cerebral mitochondrial enzyme activities.