The use of steroids to decrease the size of the infarct and the mortality in patients with acute myocardial infarction has long been the subject of controversy. In the present study, two large doses of methylprednisolone were administered intravenously to 14 patients with relatively uncomplicated myocardial infarction within 17 hours after the onset of symptoms, whereas a comparable group of 15 patients with myocardial infarction served as controls. The size of the infarct was assessed utilizing serial measurements of serum levels of creatine phosphokinase and its myocardial isoenzyme, the MB form of creatine phosphokinase. There was no significant difference between the two groups of patients with regard to peak cumulative levels of total creatine phosphokinase and the MB form of creatine phosphokinase. Similarly, there was no difference between the two groups in mortality or in the incidence of malignant ventricular arrhythmias, atrioventricular block, congestive heart failure, or extensions of the infarct. We conclude that high intravenous doses of steroids given early in the course of myocardial infarction have neither deleterious nor beneficial effects.