Cardiovascular disease is the major cause of mortality in patients receiving hemodialysis for chronic renal failure. Increased lipid peroxidation and depletion of chain-breaking antioxidants may contribute to increased risk of atherosclerosis. We have therefore assessed the effect of a single episode of hemodialysis on antioxidant status in 22 patients and control subjects. Overall, total antioxidant capacity of serum was increased in dialysis patients, but there was a marked reduction after hemodialysis [571 +/- 31 vs 342 +/- 22 mumol/L Trolox (water-soluble vitamin E analog) equivalents, P < 0.001]. The increase in total antioxidant capacity before hemodialysis was almost entirely due to relatively high serum urate. Among individual chain-breaking antioxidants, dialysis led to a decrease in urate (398 +/- 15 vs 136 +/- 12 mumol/L, P < 0.001), ascorbate (10.5 +/- 1.7 vs 5.9 +/- 1.0 mumol/L, P < 0.01), and lipid-corrected tocopherol (4.70 +/- 0.56 vs 4.26 +/- 0.39 mumol/mmol cholesterol, P < 0.05). Protein thiol groups increased after dialysis (328 +/- 16 vs 422 +/- 22 mumol/L, P < 0.001), whereas albumin remained unchanged (40.1 +/- 1.1 vs 41.0 +/- 1.6 g/L, not significant). Although total antioxidant capacity of serum is increased in hemodialysis patients, depletion of key chain-breaking antioxidants may lead to accelerated atherogenesis.