BACKGROUND The histological picture of chronic rejection with endothelial lesions and vascular hyperplasia resembles the early arteriosclerotic lesions. As increasing evidence suggests a role for oxidative stress in arteriosclerosis, we examined whether chronic rejection in renal transplant recipients was associated with increased oxidative stress markers. METHODS We investigated lipid metabolism and oxidative stress in 77 renal transplant recipients. Group I patients (n=34; 48+/-2 years old, 12 women, 22 men) had no clinical or histological signs of chronic rejection, whereas group II patients (n=43; 47+/-3 years old, 15 women, 28 men) had histologically proven chronic rejection. All patients were treated with cyclosporine and steroids. Lipid metabolism was evaluated by determining total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoproteins AI and B, and lipoprotein (a). Oxidative stress was evaluated by determining: (i) the end product of lipid peroxidation, malonyldialdehyde (MDA), and erythrocyte polyunsaturated fatty acids; (ii) the nonenzymatic antioxidant system: erythrocyte alpha-tocopherol and glutathione; and (iii) the enzymatic antioxidant system: erythrocyte superoxide dismutase and plasma glutathione peroxidase. Results were compared with those of a control group (38 healthy volunteers). RESULTS Compared with controls, renal transplant recipients had significantly increased total cholesterol, triglyceride, and apolipoprotein B levels; they also had, in association with these lipid abnormalities, a significant increase in MDA and a significant decrease in erythrocyte polyunsaturated fatty acids, as well as a significant decrease in enzymatic and nonenzymatic antioxidant defense mechanisms. In contrast to lipid disturbances, where no difference was observed between groups I and II, markers of oxidative stress were significantly higher in group II compared with group I (MDA: 1.87+/-0.43 and 1.62+/-0.31 nmol/ml, respectively, P<0.05). The red blood cell antioxidative defense mechanisms were significantly decreased in group II compared with controls (erythrocyte alpha-tocopherol: 0.61+/-0.38 and 1.08+/-0.31 mg/L, respectively, P<0.01; superoxide dismutase: 1.08+/-0.2 and 1.32+/-0.31 U/mg Hb, respectively, P<0.01). CONCLUSIONS Our data show that oxidative stress with a decrease in antioxidant defenses is associated with kidney transplantation. In addition, oxidative stress markers are particularly increased in transplant recipients with chronic rejection, which suggests that oxidative stress may participate in the development and/or progression of vascular lesions observed in these patients.