These studies determined whether superoxide dismutase (SOD), an oxygen free-radical scavenger, affects brain and lung vascular protein extravasation and water content after acute hypertension. Hypertensive vascular injury was induced in rats by bolus injection of norepinephrine. Vascular permeability was assessed with 125I-labeled serum albumin and water content determined by wet and dry weight measurement. Pretreatment with SOD prevented or reduced the increase in brain water content and brain and lung protein extravasation caused by hypertension, whereas inactivated SOD had no effect. SOD also reduced mortality caused by acute hypertension. Treatment 30 min after hypertension with SOD or polyethylene glycol-conjugated SOD reduced edema caused by hypertension. In some instances SOD reduced tissue water content and permeability to below normal control levels found in animals without hypertension. These studies show that oxygen radicals contribute to increases in permeability and water content after hypertensive injury and also suggest that oxygen radicals may contribute to regulation of vascular permeability and water content in normal animals.