Cerebral ischemia was produced by bilateral common carotid artery occlusion in female Sprague-Dawley rats. Ranitidine, a histamine H2 receptor blocking agent, given intraperitoneally 30 min prior to ischemia, exerted a dose-dependent protective effect on water accumulation and ion shifts in the brain (Na+, K+ and Ca2+). To decide whether ranitidine can prevent ischemia-induced brain edema when given in the postischemic period, ranitidine (10 mg/kg i.p.) was administered 1, 2, and 3 h respectively after the onset of cerebral ischemia. Early (1 h) postocclusion treatment was still able to attenuate the ischemia-induced water accumulation and maldistribution of ions in the brain tissue.