The effects of recombinant human erythropoietin (rHuEPO) on plasma and peritoneal effluent levels of antithrombin III (AT-III), protein C (PC) activity and protein S (PS) activity were evaluated in 10 uremic children or? continuous ambulatory peritoneal dialysis (CAPD). The findings were compared with values obtained from ten healthy children. Levels of AT-III and of PC and PS activity in plasma ar td peritoneal effluent were measured before, and at 8 and 12 weeks after; rHuEPO treatment. Baseline levels of AT-III and PC activity in plasma were lower than the control values. Levels of PC activity increased during the trial, while levels of AT-III remained unchanged, and levels of PS activity decreased. Baseline levels of PC activity in peritoneal effluent were lower than those obtained during rHuEPO treatment, while no change in peritoneal levels of PS activity and AT-III was observed after rHuEPO treatment. A significant positive correlation was seen between plasma and peritoneal levels of PC activity at baseline. A significant positive correlation was also seen between? plasma levels of PS activity and hemoglobin at week 12, and a significant negative correlation between plasma levels of AT-III and albumin at week 8. No correlation was found between the plasma natural coagulation inhibitors and CAPD duration. These results suggest that plasma PS activity cart be decreased, and plasma PC activity increased, by rHuEPO treatment in children.