BACKGROUND: This study was conducted to determine the effects of dexamethasone and MK-801 on the formation of brain edema resulting from a focal ischemic injury by middle cerebral artery occlusion in rats. METHODS: Fifteen Sprague-Dawley rats (220 280 g) were freely allowed to drink and eat until just before surgery. Anesthesia was induced with 4% isoflurane in oxygen and then maintained with 2% isoflurane in oxygen. Ischemic injury was induced by an intraluminal suture with a blunted tip inserted into the internal carotid artery and occlusion of the middle cerebral artery. All rats were divided randomly into three groups. In group I (n = 5), normal saline 1 ml was injected intravenously 10 minutes before MCA occlusion. In group II (n = 5), dexamethasone 3 mg/kg was administered 10 minutes before injury. In group III (n = 5), a N-methyl-D-aspartate receptor antagonist, MK-801 1 mg/kg was injected 30 minutes before injury. Rectal temperatures were monitored during the experiment. After 60 minutes of MCA occlusion, the intraluminal sutures were removed and all the rats were returned to their cages. Their brain were quickly removed and the cerebral hemispheres were sepaerated into ischemic cores and penumbra zones after 1 hour of reperfusion. The separated cerebral hemispheres were dried 7 days at 60oC dry oven. The cerebral water content was assessed by the dry-weight method. RESULTS: In the dexamethasone group, there were no significant changes in cerebral edema formation in both ischemic core and the penumbra. In the MK-801 group, there were significant reductions in the brain edema formation in the penumbra (P< 0.05), but not in the core. CONCLUSIONS: Dexamethasone has no effect on ischemic brain edema; however, MK-801 is effective in the ischemic penumbra zone by reducing of edema formation.