Acute mesenteric ischemia is highly lethal and therefore a serious problem for surgery and intensive care medicine; accordingly its pathophysiology warrants further study. Oxygen free radicals (OFR) play a role in the intestinal mucosal damage that develops during reperfusion after ischemia. Histamine (H) is generally released in various types of tissue ischemia. The link between H release and OFR has only been studied in in vitro systems. We tested the hypothesis that OFR may be involved in H release following reperfusion of the ischemic gut. The artery supplying a segment of the ileum was occluded for 1 or 2 h in anesthetized dogs. On reperfusion, a release of H into the venous effluent of the segment was demonstrated. Pretreatment of the animals with allopurinol (an inhibitor of xanthine oxidase), or with MTDQ-DA [6,6’-methylenebis(2,2-dimethyl-4-methanesulfonic acid sodium-1,2-dihydroquinoline)], a superoxide anion scavenger, or with a combination of allopurinol and MTDQ-DA resulted in an inhibition of H release. We conclude that OFR may play a role in the local H release following intestinal ischemi