Thrombin-antithrombin III complex (TAT) is a marker of thrombin generation, indicating increased coagulability. To investigate whether paroxysmal atrial fibrillation (PAf) is associated with an increased coagulation system, we measured TAT within 24 h after the documentation of PAf in 50 patients with structurally normal hearts. The mean age of the study population was 62 years old. In 32 patients, PAf was documented during routine physical examinations, electrocardiograms or echocardiograms and in the remaining 18 patients, it was reproducibly documented on more than two Holter electrocardiograms. Group I consisted of 38 TAT data sets from 38 patients who did not receive anticoagulant therapy during PAf episodes. At least one week after starting anticoagulant therapy, TAT was measured again in ten patients in whom there was evidence of PAf on the day of measurement. In the remaining 12 patients, PAf occurred while the patients were receiving anticoagulation. Group II consisted of 22 TAT data sets from 22 patients who received anticoagulation during PAf episodes. The average TAT value was 5.8 ng/ml in group I, while it was 2.8 ng/ml in group II (P<0.0001). TAT was greater than 5 ng/ml in 15 of the 38 patients in group I, and in four of the 22 patients in group II. In 20 symptomatic patients, we measured TAT again when the patients maintained sinus rhythm under the same anticoagulant therapy; four patients were receiving and 16 patients were not receiving anticoagulation therapy. TAT decreased from 6.4 to 2.3 ng/ml on average when PAf disappeared and sinus rhythm was maintained (P=0.0009). Increase in the coagulation system occurred transiently during or shortly after PAf episodes in about 40% of PAf patients. As patients with prior anticoagulation had a relatively low TAT value, anticoagulant therapy might be useful in patients with PAf.