The kidney is probably the major site of production of the plasma enzyme glutathione peroxidase (GSHPx-P). For this study, GSHPx-P activity was determined in 40 healthy people, in 34 patients with differing degrees of renal impairment, and in hemodialysis patients from whom blood samples were withdrawn either before or after each session (18 patients) or throughout the dialysis session (27 patients). Hemodialysis patients were treated by means of different techniques (bicarbonate hemodialysis, hemodiafiltration, and acetate free biofiltration), and different membranes (cuprophane, polyacrylonitrite, and polymethylmethacrylate). The following results were obtained: 1) GSHPx-P activity was significantly decreased in renal impairment patients; 2) GSHPx-P activity negatively correlated with serum creatinine values in renal impairment patients (r= −0.55; p < 0.001); and 3) the enzyme activity slightly increased after the session in hemodialysis patients. The following conclusions can be drawn: GSHPx-P activity could be a new index of renal function, because it was decreased in patients with renal failure; the decrease in GSHPx-P activity paralleled the severity of renal impairment, and was maximal in hemodialysis patients; GSHPx-P activity was slightly raised at the end of the hemodialysis session, concomitant with other enzyme activities (aspartate transaminase, alanine transaminase, and alkaline phosphatase) and total protein concentration. This seems to be attributable to the process of water loss rather than other hypothetical mechanisms, such as A) enzyme activation by either peroxide generation during blood-membrane contact, or by the removal of a hypothetical inhibitor; and B)de novosynthesis in the residual renal mass or in other sites of production.ASAIO Journal1994; 40:968-971.