Whether ‘malignant’ brain edema following ischemic stroke is due to or aggravated by reperfusion and therefore more frequent after thrombolytic therapy of stroke is still under debate. From 3/96 to 1/97, we treated 51 patients with acute supratentorial stroke within 3 h after symptom onset with rt-PA following a protocol similar to the NINDS study. The results of thrombolytic therapy were evaluated by repeated clinical examination and computed tomography (CT) during the first week after ictus. The incidence of space-occupying brain edema following intravenous thrombolytic therapy of acute ischemic stroke was lower than the edema frequency after conventional treatment, but mortality from ‘malignant’ edema was higher in the patients with thrombolysis. Thus, space-occupying edema after acute ischemic stroke may be aggravated by thrombolytic treatment. Forced reperfusion of already irreversibly damaged tissue increases edema formation and enlarges developing infarcts with a deleterious increase of intracranial pressure.