Previous reports indicate that allopurinol, a xanthine oxidase inhibitor, largely prevents the injury produced by reperfusion of ischemic tissues. In order to further assess the role of xanthine oxidase in ischemia-reperfusion injury, we examined the influence of another inhibitor of the enzyme (pterin aldehyde) on the increased vascular permeability produced by intestinal ischemia. Vascular permeability estimates in autoperfused segments of cat ileum were derived from the relationship between lymph-to-plasma protein concentration ratio and lymph flow. One hour of intestinal ischemia increased vascular permeability to 0.43 +/- 0.02 from a control (nonischemic) value of 0.08 +/- 0.005. In ischemic ileal segments pretreated with purified pterin aldehyde, vascular permeability increased to only 0.15 +/- 0.02. Pretreatment with commercially prepared folic acid, which is contaminated with pterin aldehyde, also attenuated the ischemia-induced increase in vascular permeability (0.16 +/- 0.04). These findings support the hypothesis that xanthine oxidase is a major source of oxygen-free radicals produced during reperfusion of the ischemic small bowel.