Our study describes the anatomy of the middle cerebral artery (MCA) in 65 Sprague-Dawley rats and the spatial distribution of ischemic cortical lesions caused by occluding major MCA branches. The rats characteristically had at least two major MCA branches, frontal and parietal. Many rats had additional branches supplying the pyriform and temporal cortexes. Permanent occlusion of the frontal or parietal branches combined with 30 minutes of bilateral carotid artery occlusion produced visible Evans blue dye uptake by ischemic cortical areas after 24 hours. No lesions distal to the occlusion were apparent in 38% and 43% of rats with frontal and parietal branch occlusions, respectively; small lesions contiguous with the occlusion site were observed in 38% and 32% of the rats. Only 6% of the frontal and 7% of the parietal branch occlusions produced isolated distal infarcts as expected if these branches were end-arteries. Blood flow was reversed in arteries distal to the occlusion. We conclude that extensive collateral connections of the frontal and parietal MCA branches with other arterial systems protect the anterior and posterior cortical regions. In contrast, occlusions of the pyriform branch of the MCA invariably caused infarcts in the frontopyriform region. In about one third of the rats, frontal or parietal branch occlusions produced lesions involving much of the proximal MCA territory; the frontopyriform region was most consistently affected. Combined, these data suggest that the pyriform MCA branch is an end-artery and that the cortical region it supplies is prone to ischemic damage resulting from any reduction of blood flow through the main MCA trunk.(ABSTRACT TRUNCATED AT 250 WORDS)