The aim of the present study was to determine the potential therapeutic value of 21-aminosteroid U-74389G, on blood-brain barrier (BBB) breakdown and edema in association with the changes in synaptosomal Na+/K+ and Mg2+/Ca2+-ATPase activities in rat brain subjected to post-ischemic reperfusion injury. Brain ischemia was achieved by means of four-vessel occlusion model for 25 min and animals were sacrificed after 12 h reperfusion. An increase of cerebral tissue water content, blood-brain disruption and the changes of synaptosomal Na+/K+ and Mg2+/Ca2+-ATPases activities were evaluated. U-74389G was given intraperitoneally at two times as 5 mg/kg at 10 min prior to ischemia and at the beginning of reperfusion. Edema was determined by means of wet-dried weight method, and BBB of extravasation of Evan's blue dye.