Tissue damage in ischemia/reperfusion injury may be mediated by oxidative stress caused by reactive oxidant species. Since such reactive species are difficult to measure directly, changes in antioxidant concentrations are often used as an indication of oxidative stress, In this study, microdialysis membranes were inserted into the livers of anesthetized rats to determine the effects of ischemia/reperfusion on the extracellular concentrations of two antioxidants, uric acid and ascorbic acid, Total hepatic ischemia was induced for 30 min by clamping the portal triad and was followed by 60 min of reperfusion, Uric acid and ascorbic acid concentrations were measured in microdialysis perfusates by high-performance liquid chromatography with electrochemical detection. Initial uric acid and ascorbic acid concentrations were high after insertion of membranes into the liver and decreased rapidly within 90 min (P < 0.001; ANOVA with repeated measures), Uric acid concentrations increased over 300% after ischemia and by 600% during the first 30 min of reperfusion (n = 8; P < 0.05). Ascorbic acid concentrations were 60% higher than controls after ischemia and 90% higher during the first 30 min of reperfusion (n = 8; P < 0.05), Alterations in concentrations of these redox-active molecules may be associated with oxidative stress in liver extracellular fluid during ischemia/reperfusion. (C) 1996 Academic Press, Inc.