T2*-sensitive echo-planar magnetic resonance imaging was used with first-pass magnetic susceptibility contrast enhancement in a cat model of acute regional stroke to evaluate the relationship between cerebral hypoperfusion and ischemic brain damage. In normal brain, dose-dependent decreases in signal intensity were observed after intravenous injection of 0.15-0.50 mmol/kg dysprosium-diethylenetriaminepentaacetic acid bismethylamide or gadodiamide injection. Shortly after unilateral occlusion of the middle cerebral artery, foci of signal hyperintensity on diffusion-weighted images were observed in the ipsilateral basal ganglia. Sixty minutes after occlusion, perfusion deficits in the ipsilateral parietal and temporal cortical gray matter were observed to be spatially correlated with areas of hyperintensity on diffusion-weighted images. When reflow was attempted after 60 minutes, delayed contrast agent transit suggestive of partial ischemic tissue injury was demonstrated. Attempts to produce reflow after 2 hours did not restore normal brain perfusion and resulted in image hyperintensity and histopathologic brain damage. Six-hour occlusion was associated with pronounced perfusion deficits in the ischemic territory.