Cardiovascular disease is the major cause of morbidity and mortality in patients with end-stage renal failure. Increased free radical production and antioxidant depletion may contribute to the greatly increased risk of atherosclerosis in these patients. Glutathione peroxidase (GPX) is an important antioxidant, the plasma form of which is synthesized mainly in the kidney (eGPX). The aim of this study was to assess the activity of eGPX in patients with end-stage renal failure on haemodialysis. Venous blood was collected from 87 haemodialysis patients immediately prior to and after dialysis and from 70 healthy controls. Serum eGPX activity was measured using hydrogen peroxide as substrate and immunoreactivity determined by ELISA. eGPX activity was significantly reduced in dialysis patients when compared to controls (106 ± 2.7 and 281 ± 3.6 U/l respectively, p < 0.001). Following haemodialysis, eGPX activity rose significantly to 146 ± 3.8 U/l, p < 0.001, although remaining below control values (p < 0.005). Immunoreactive eGPX, however, was similar in all groups (pre-dialysis 14.10 ± 1.26 µg/ml, post-dialysis 14.58 ± 1.35 µg/ml, controls 15.20 ± 1.62 µg/ml, p = NS). A decrease was observed in the specific activity of eGPX in patients when compared to controls (8.81 ± 1.14, 10.71 ± 1.54 and 21.97 ± 1.68 U/mg respectively, p < 0.0001). eGPX activity is impaired in patients undergoing haemodialysis and so may contribute to atherogenesis in renal failure.