Antithrombin III levels were studied in relation to the occurrence of thromboembolism in 48 patients with various degrees of proteinuria. Nine of these patients had clinical signs of thrombosis, including four with renal vein thrombosis. In eight of these nine patients, antithrombin III concentrations were below 70 per cent. There was a significant negative correlation between the antithrombin III concentration and the urinary protein excreation (P less than 0.001). Antithrombin III was found in the urine of 32 of 42 patients. There was a significant correlation between the renal clearance and the degree of antithrombin III serum deficiency (P less that 0.001). The clearance and serum level of albumin closely paralleled these changes. We conclude that thrombosis in patients with severe proteinuria is associated with a deficiency of antithrombin III due to urinary excretion of this protein.