Although animal models have demonstrated that late secondary cerebral injury after arterial occlusion and subsequent recanalization may limit the benefit of reperfusion therapy, this phenomenon has not been well characterized in humans. Diffusion-perfusion magnetic resonance imaging studies were performed before treatment, early after treatment, and at day 7 in patients undergoing vessel recanalization with intraarterial thrombolytics. Among 18 patients studied, mean age was 71 (range, 27-94), and median entry National Institutes of Health Stroke Scale score was 13 (range, 6-25). Early after recanalization, partial or complete normalization of diffusion imaging abnormalities occurred in 8 of 18 (44%) patients. Among the eight patients with early diffusion imaging reversal, late secondary injury by day 7 occurred in 5 (63%), and sustained normalization of all reversed tissue occurred in 3 (38%). Pretreatment apparent diffusion coefficient values were lowest in regions experiencing no reversal (mean apparent diffusion coefficient, 608 microm(2)/sec), intermediate in regions with reversal and secondary decline (617 microm(2)/sec), and highest in regions with sustained reversal (663 microm(2)/sec). There was a trend toward less improvement in neurological deficit in patients with secondary injury versus patients with sustained reversal. In the future, late secondary tissue injury may become an important therapeutic target for postreperfusion neuroprotective therapies, with treatment efficacy monitored by serial diffusion magnetic resonance imaging.