Mucosal albumin clearance was measured in jejunal segments of dogs under control conditions, after arterial occlusions of varying duration (15 min-4 h), and during intraluminal perfusion with hypoxanthine-xanthine oxidase. Albumin clearance rates were estimated from the luminal perfusion rate and the activity of protein-bound 125I in the perfusate and plasma. Arterial occlusion of 30-min to 4-h duration produced a significant increase in mucosal albumin clearance. The magnitude of the rise in albumin clearance was directly related to the duration of arterial occlusion. Pretreatment with superoxide dismutase, a superoxide radical scavenger, or allopurinol, a xanthine oxidase inhibitor, did not prevent the increased albumin clearance induced by 1 h of occlusion. Intraluminal perfusion with hypoxanthine-xanthine oxidase significantly increased mucosal albumin clearances. This increase was prevented by superoxide dismutase. The results of this study indicate that arterial occlusions and enzymatically generated superoxide radicals increase mucosal albumin clearance.