It has been suggested that hemodialysis patients may be under increased oxidative stress and may therefore benefit from the long-term use of antioxidants (particularly for the reduction of the risk of heart disease). The aim of this study was, first, to evaluate the effect of hemodialysis by itself on lipid and lipoprotein oxidation profiles and, second, to analyze the effect of vitamin C supplementation in patients with end-stage renal disease starting hemodialysis. Forty-one patients with end-stage renal disease were enrolled and randomized to receive 1000 mg/d vitamin C or matching placebo before starting hemodialysis. We measured lipid profile and the susceptibility of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) to oxidation using copper ions at the moment of inclusion and after 1 year. All lipoperoxidation parameters were included. Hemodialysis by itself improved the lipid profile, lowering total cholesterol (176.4 +/- 48.4 to 154.2 +/- 28.8 mg/dL, P < .01), LDL cholesterol (94.1 +/- 39.6 to 76.1 +/- 26.6 mg/dL LDL, P < .03), and phospholipids levels (196.5 +/- 36.7 to 182.9 +/- 36.1 mg/dL, P < .05) in all patients on maintenance hemodialysis. The HDL cholesterol was also decreased (49.4 +/- 19.8 to 43.4 +/- 24.1 mg/dL HDL, P < .03). No significant differences were detected between patients receiving vitamin C and those receiving placebo. Thiobarbituric acid reactive substances (TBARS) and lipoperoxides increased in patients after a year of hemodialysis, but the difference was lower in those administered vitamin C for a year-TBARS LDL (in nanograms per gram LDL): 0.25 +/- 0.20 to 0.38 +/- 0.2 in vitamin C-treated subjects and 0.28 +/- 0.17 to 0.46 +/- 0.21 in those treated with placebo (P < .007); TBARS HDL (in nanograms per gram HDL): 0.22 +/- 0.12 to 0.34 +/- 0.30 in patients receiving vitamin C and 0.20 +/- 0.18 to 0.28 +/- 0.19 in those receiving placebo (P = .071). Hemodialysis by itself seems to improve the lipid profile in patients with a previous prooxidative state such as uremia. Although our results failed to demonstrate significant differences between vitamin C-treated and untreated patients, and despite the small number of patients, the trend toward a decrease in oxidation products due to vitamin C supplementation may be beneficial for oxidation parameters. This area remains controversial and under active investigation. Further research is necessary before a firm conclusion can be reached.