In the search for a more reproducible focal ischemic stroke model in the rat, we systematically interrupted blood flow to the right middle cerebral artery territory by ligating the right middle cerebral artery, and the right and left common carotid arteries in succession. Using a laser-Doppler flowmeter, we found that the relative surface blood flow in cerebral cortex supplied by the right middle cerebral artery decreased to 62, 48, and 18% of baseline respectively after successive ligation of the right middle cerebral artery, and the right and left common carotid arteries. A focal infarct in the cerebral cortex supplied by the right middle cerebral artery was consistently noted after ligation of the right middle cerebral and the right common carotid arteries and temporary clip occlusion of the left common carotid artery for 60 min. The surface areas of infarction measured 100 +/- 6 mm2 and the maximal cross-sectional area of infarction was 10.4 +/- 1.1 mm2 (N = 10). The mortality rate was 7% (N = 70). The characteristic changes of ischemic necrosis were limited to the cortex with sparing of subcortical structures. No motor deficits occurred. Occlusion of the right middle cerebral artery alone or together with the right common carotid artery did not consistently cause gross infarction and the maximal cross-sectional area of infarction was smaller (the right middle cerebral artery, 1.7 +/- 0.8 mm2, N = 10; the right middle cerebral artery plus the right common carotid artery, 4.8 +/- 1.9 mm2, N = 10). Permanent ligation of the right middle cerebral artery and both common carotid arteries had a high mortality (60% in 3 days, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)