Plasma antithrombin (AT) measured as heparin cofactor activity decreased 0.16 +/- 0.13 U/ml (mean +/- SD) in 198 patients who received heparin infusion during 1 wk for deep venous thrombosis (DVT). The decrease was weakly, but significantly correlated to heparin dose (r = 0.15, p = 0.02) and to heparin plasma concentration (r = 0.12, p = 0.05). In patients with subnormal AT at start of heparin treatment, AT decreased less and tended to normalize at the end of heparin infusion, suggesting increased synthetic rate. The decrease in AT was apparently unrelated to the extension or the fate of the thrombus, and also unrelated to other patient and disease characteristics apart from a significantly higher decrease in diabetics. 5 out of 9 patients with AT values below 0.60 U/ml had serious disease, and 1 died from pulmonary embolism (PE) shortly after cessation of heparin (AT 0.22 U/ml). We conclude that the main decrease in AT occurs during the initial 3 d of heparin treatment. If AT stays above 0.70 U/ml after 3 d of treatment, further AT monitoring is hardly indicated.