Obesity-associated alterations in coagulation and fibrinolytic factors in favor of thrombosis are well known. Observations suggest that leptin, a recently discovered obesity gene product, in addition to being a satiety factor, induces platelet aggregation, accelerates formation of firm thrombi, and is associated with abnormal fibrinolysis. The authors studied the influence of plasma leptin concentrations on admission within 6 hours of acute myocardial infarction (MI) on the outcome of thrombolytic therapy (TT). Forty-one patients with acute MI who underwent TT were enrolled into the study. Levels of plasma leptin were determined with radioimmunoassay method in samples obtained just before initiation of TT. Patients were initially classified according to the admission plasma leptin concentrations, and it was observed that failure of reperfusion therapy with streptokinase was significantly higher in patients with admission plasma leptin concentrations > or =14 ng/mL (group 2) as compared to patients with admission plasma leptin concentrations <14 ng/mL (group 1). Final failure of TT, identified both by reinfarction and absence of early reperfusion as assessed noninvasively, was observed in 11 patients (39%) in group 1 and in 10 patients (77%) in group 2 (p=0.025). Left ventricular ejection fraction was slightly but significantly higher in group 1 than in group 2 (p=0.031). High plasma leptin concentrations on admission in patients within 6 hours after the onset of acute MI are associated with less TT efficacy. The authors suggest that admission leptin levels may play a role in the management of patients with acute MI.