Objectives. This study investigated the influence of early spontaneous intermittent reperfusion on the extent of myocardial damage and its relation to endogenous hemostatic activity, Background. In the early phase of acute myocardial infarction coronary occlusion is often intermittent, even before thrombolytic therapy is administered. The relation between this phenomenon, myocardial damage and hemostatic activity is unknown. Methods. Holter ST segment recording and pretreatment plasma tissue type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, prothrombin fragment F1+2 and soluble fibrin levels were measured in 57 patients with acute evolving myocardial infarction. Spontaneous intermittent myocardial reperfusion, defined as two or more episodes of transient resolution of ST segment elevation to within 0.05 mV of baseline, lasting ≥1 min, before the start of recombinant t-PA (rt-PA) treatment was present in 28 patients (group 1) and absent in 29 (group 2). Left ventriculography and coronary angiography were performed 90 min after intravenous rt-PA administration. Plasma creatine kinase-MB fraction (CK-MB) levels were measured every 6 h for 24 h, and C-reactive protein levels were measured daily for 3 days. Results. Group 1 had lower peak plasma CK-MB (141.9 ± 28.3 vs. 203.8 ± 23.3 IU/liter [mean ± SEM], p < 0.014) and C reactive protein levels (16 ± 4 vs. 28 e 4 mg/liter on day 1; 26.6 ± 5.5 vs. 61.8 ± 14.4 mg/liter on day 2; 19.6 ± 4.2 vs. 40.6 ± 6.5 mg/liter on day 3, p < 0.012) and a higher left ventricular ejection fraction (62.9 ± 4% vs. 51.1 ± 5%, p < 0.04) than group 2. Group 1 had lower plasma t-PA antigen levels (15.6 vs. 27 μg/liter, p < 0.006) but higher prothrombin fragment F1+2 (1.8 vs. 1.1 nmol/liter, p < 0.003) and soluble fibrin levels (66.8 vs. 31 nmol/liter, p < 0.01). Coronary patency at 90 min was similar. Conclusions. Early spontaneous intermittent reperfusion during acute myocardial infarction is associated with augmented thrombogenic activity and less subsequent myocardial damage, This finding is consistent with a protective effect of intermittency on the myocardium and a procoagulant effect of spontaneous lysis on blood. It may also reflect a different rate of evolution of coronary thrombosis and myocardial infarction in patients with and those without spontaneous intermittent myocardial reperfusion.