Fifty-four consecutive patients with acute anterior myocardial infarctions were studied to determine the incidence and natural history of mural thrombus formation. Two-dimensional echocardiography was performed in the immediate postinfarction period. Multiple views were utilized. Standard criteria for defining mural thrombus formation and minimizing false-positive readings were adhered to. Correlation with clinical data was obtained in all patients to define a subgroup at high risk for the development of a mural thrombus. Follow-up was obtained for all patients to assess the natural history of mural thrombus formation, treated and untreated, with regard to peripheral embolization. Seventeen patients (32 percent) had mural thrombus formation. Statistically significant (p less than 0.001) correlation for mural thrombus formation was found with markedly elevated creatine kinase and lactate dehydrogenase levels and with apical dyskinesis. Ten patients with mural thrombi received anticoagulation therapy. None has had clinically evident emboli at a mean of 10.8 months follow-up. Resolution of the mural thrombus was demonstrated with serial two-dimensional echocardiography in eight patients (80 percent). Six of seven patients who did not receive anticoagulation therapy (86 percent) had embolic events within three months (p less than 0.001). None of the 36 patients without a mural thrombus has had a spontaneous clinical embolus. Thus, the presence of a mural thrombus can be accurately identified in patients with acute myocardial infarction and predicted in a subgroup of those patients. Such patients should be considered for anticoagulation to prevent systemic embolization and should be followed with serial two-dimensional echocardiography.