Liver ischemia followed by reperfusion is an important and common clinical event associated with the activation of an endogenous inflammatory response. The aim of this study was to determine the effects of cyclosporin A (CsA) and ibuprofen (IBU) on ischemia-reperfusion injury. Male Spraque-Dawley rats were subjected to 60 min of total liver ischemia followed by 120 min reperfusion. Liver tissue samples were obtained for measurements of malondialdehyde (MDA) levels as an index of tissue lipid peroxidation by thiobarbituric acid assay. Three groups of animals were pre-treated with CsA or IBU or both. Treatment with these agents was given at onset reperfusion after ischemia. The other groups were designated as ischemic controls, non-ischemic controls and reperfusion group without treatment. Ischemic control animals showed increased liver MDA levels and in the reperfusion group MDA levels were significantly higher than ischemic levels. CsA and IBU-treated animals had better survival and diminished liver MDA levels. The most significant decrease MDA levels was observed in the group treated with two agents which were given together. Serum enzyme levels were significantly higher in the reperfusion group than in the ischemic controls and the enzyme levels were significantly diminished after the treatments. This study suggests that CsA and IBU may be important agents in modulating lipid peroxidation in ischemia-reperfusion liver injury, and combined therapy with these agents may be more effective in treatment of ischemia-reperfusion injury, (C) 1998 Elsevier Science B.V. All rights reserved.