Atherosclerotic cardiovascular disease is the leading cause of death in patients with end stage renal disease (ESRD) who have undergone dialysis treatment. The oxidation of low density lipoprotein (LDL) appears to be a crucial step in the pathogenesis of atherosclerosis. The increased oxidative stress and attendant increased oxidizability of lipoproteins, such as LDL could contribute to the accelerated atherosclerosis in dialysis patients. Since alpha-tocopherol (AT) is the major antioxidant in LDL, the aim of the present study was to test the effectiveness of RRR-AT supplementation (800 I.U. per day) for 12 weeks on the susceptibility of LDL to oxidation. The study subjects comprised patients with chronic renal failure on hemodialysis (HD), peritoneal dialysis (PD), and age and sex matched controls (C). Plasma fatty acids, lipoproteins and AT levels were measured in these subjects before and after supplementation. Also, LDL AT and oxidizability was studied. LDL was isolated by ultracentrifugation at baseline and after 12 weeks of supplementation, and subjected to a 5-h time course of copper catalyzed oxidation. Oxidation was measured by the formation of conjugated dienes (CD) and lipid peroxides (LP). Supplementation with AT did not alter the plasma lipid or lipoprotein profile of these subjects. Plasma lipid-standardized AT and LDL AT concentrations were not different among the groups at baseline. AT supplementation significantly increased plasma lipid-standardized AT (C=150%, HD=149%, PD=217%, P<0.001) and LDL AT concentrations (C=94%, HD=94%, PD=135%, P<0.003). AT enrichment of LDL resulted in a significant prolongation in conjugated diene lag phase in all groups (C=34%, HD=21%, PD=54%, P<0.02). Lipid peroxide lag phase was also increased significantly in C (27%,) and PD (40%) groups after AT supplementation (P<0.01). There was a significant positive correlation between plasma lipid standardized AT and lag phase (r=0. 54, P=0.0003). Overall, AT decreased the susceptibility of LDL to oxidation in patients with chronic renal failure but the benefit appears to be greater in patients on PD. Therefore, AT supplementation may also provide a measure of protection against CAD in patients with chronic renal failure on dialysis therapy.