Heparin cofactor II (HCII) is a thrombin inhibitor in human plasma which displays similarities with antithrombin III (ATIII). Hereditary HCII deficiency was recently reported to be associated with thrombophilia. Since thromboembolism constitutes one of the main complications of the nephrotic syndrome (NS), both activities and antigen concentrations of HCII and ATIII were measured in the plasma and urine of 33 adult patients with nephrotic syndrome. The mean HCII plasma level was significantly increased whereas the ATIII level was decreased. Plasma HCII was significantly correlated with proteinuria and with the fibrinogen level, suggesting that HCII could act as an acute phase reactant in patients with NS. HCII antigen was detectable in 16 of the 24 available urine samples, whereas ATIII antigen was present in all of them. In addition, functionally active HCII was detected in most of the urine samples containing HCII antigen, while ATIII was only present in the inactive form. In conclusion, these findings suggest that HCII is submitted to a metabolic pathway different from that of ATIII in patients with NS.