Prospective evaluation of platelet activation and hypercoagulability was performed in 31 patients with Kawasaki syndrome. Most patients had elevated acute-phase reactants when studied during the first 3 weeks of their illness; 17 of 25 (68%) patients had factor VIII activity >150%, 18 of 24 (75%) had fibrinogen >400 mg/dl, and 17 of 31 (55%) had a platelet count >450.000/mm³. Antithrombin III was depressed initially in 17 of 25 (68%) patients. Depleted fibrinolytic activity, as measured by a euglobulin lysis time >300 minutes, was documented in nine of 20 (45%) patients. Plasma β-thromboglobulin (BTG) measured at 0 to 3 weeks was elevated (>43 ng/ml) in seven of 24 (29%) patients. All patients with coronary artery aneurysms had elevated BTG values. The mean BTG in the group with aneurysms was 72.3 ng/ml when measured during the first 3 weeks after onset of fever, and 87.7 ng/ml at 4 to 7 weeks. The group without aneurysms had mean BTG values of 29.4 and 28.3 ng/ml at 0 to 3 and 4 to 7 weeks, respectively. The difference between the two groups was significant (P<0.002) for both the initial and later values. An elevated BTG during the first 3 weeks after onset of fever was highly associated with aneurysm formation in our patients (P<0.007). No aneurysms occurred in patients with a normal BTG value.