The endothelial and smooth muscle integrin alphaVbeta3, a receptor for vitronectin and fibrinogen, participates in angiogenesis associated with wound healing and tumorigenicity. The microvascular expression of alphavbeta3 and fibrin during experimental middle cerebral artery occlusion and reperfusion in a nonhuman primate model was examined by computer-assisted video imaging microscopy. No microvascular expression of alphavbeta3 was seen in the control subjects (n = 3) or the non-ischemic basal ganglia of subjects undergoing 2-hour MCA:O (middle cerebral artery occlusion) or 3-hour occlusion with 1-hour (n = 3), 4-hour (n = 3), and 24-hour (n = 3) reperfusion. In the ischemic territory, alphavbeta3 appeared initially at 2 hours of middle cerebral artery occlusion. Up-regulation of alphavbeta3 was confined to the media of 30.0- to 50.0-micron-diameter arterioles in the ischemic core and correlated significantly with fibrin deposition in those vessels (P < 0.0005). Integrin alphavbeta3 and its ligand fibrinogen appear in a subpopulation of microvessels after focal cerebral ischemia.