Heparin cofactor II (HC II) is a plasma glycoprotein which inhibits thrombin but not factor Xa and which requires heparin or other glycosaminoglycans for its activation. Although several pedigrees have been reported in which 50% decreases in plasma HC II were associated with venous or arterial thrombosis, the role of HC II deficiency in inherited thrombophilia remains unproved. The present study was performed to determine the prevalence of HC II deficiency among patients with a history of venous thrombosis. HC II antigen was measured by electroimmunoassay in 122 unrelated patients with first episode of deep vein thrombosis developed before the age of 45 and in 114 healthy volunteers. Of the controls, 1 had a low HC II concentration (37%), while in the remaining 113, levels ranged from 65 to 180% with the mean value of 98.6 +/- 20.6%. In thrombosis patients, the mean HC concentration was 99.9 +/- 28.0%: individual values ranged from 52 to 180%. Seven patients (5.7%) exhibited values beneath the lower limit of the normal range (65%). These results indicate that HC II deficiency is more prevalent among patients with venous thromboembolism than in healthy subjects.