Patients undergoing dialysis are subject to risk of thrombotic complications. We studied the plasma levels of natural coagulation inhibitors including protein C (PC), protein S (PS), and antithrombin III (AT III) in 20 patients on hemodialysis and 20 patients on continuous ambulatory peritoneal dialysis (CAPD). Total PS antigen, free PS antigen, immunological and functional activities of PC and AT III were measured. Hemodialysis patients had a higher total PS level but a lower free PS level compared with healthy controls. Both the immunological and functional activities of AT III in hemodialysis patients were significantly lower than those of controls. With the exception of total PS level, CAPD patients had comparable or even higher plasma level of natural coagulation inhibitors compared with healthy controls. Furthermore, the plasma levels of PC, PS, and AT III were significantly lower in hemodialysis patients compared with CAPD patients despite greater daily losses of PC, PS, and AT III through urinary and peritoneal routes in patients on CAPD treatment. Most of the AT III in the peritoneal dialysate was still functionally active but most of the PC was inactive. Our observations suggest an effective turnover and production of these natural coagulation inhibitors in patients on CAPD therapy but a similar compensatory mechanism does not operate efficiently in patients receiving hemodialysis.