High-density lipoprotein (HDL) has been shown to prevent the oxidation of low-density lipoprotein (LDL). The antioxidant activity of HDL is believed to reside in its enzymes, particularly paraoxonase. Recently, paraoxonase (PON) has been implicated in the pathogenesis of atherosclerosis. We have examined the activity, and phenotype distribution of serum PON in 76 patients with chronic renal failure undergoing maintenance hemodialysis as patient group and 66 healthy subjects as control group. The serum paroxonase activity in this patient group were significantly reduced when compared to the control group (p<0.0001). The levels of HDL and apolipoprotein A1 (Apo-A 1) in the patient group were also lowest when compared to the control group (p<0.0001 and p<0.0001, respectively). The PON activity for HDL (PON/HDL ratio) and apoAl (PON/ Apo-Al ratio) levels in the patient group were significantly reduced when compared to the control (p<0.0001) and p<0.0001, respectively). The phenotypic distribution of PON (AA,AB,BB) was not significantly different between patient and the control groups. We conclude that serum paraoxonase activity was significantly lower in the chronic hemodialysis patients as independent of paraoxonase phenotypic.