The Intravenous Streptokinase in Acute Myocardial Infarction (I.S.A.M.) trial was a prospective, placebo-controlled, double-blind multicenter trial of high-dose short-term intravenous streptokinase in acute myocardial infarction administered within 6 h after the onset of symptoms. Global and regional left ventricular ejection fractions were determined by radionuclide ventriculography in a subset of 120 patients 3 days, 4 weeks, 7 months, 18 months and 3 years after acute myocardial infarction. In patients with anterior myocardial infarction, left ventricular ejection fraction was higher in the streptokinase than in the placebo group 3 days after acute infarction (49 +/- 14% vs. 40 +/- 11%, p = 0.02). This difference of about 10% units in ejection fraction persisted during the 3 year follow-up period. Among streptokinase-treated patients, regional left ventricular ejection fraction was higher within the infarct zone as well as in remote myocardium throughout the follow-up period. Among patients with inferior infarction, no significant differences between the treatment and control groups were demonstrable with respect to global and regional left ventricular ejection fraction. Thus, intravenous administration of streptokinase within 6 h after the onset of symptoms of acute myocardial infarction preserves left ventricular function over a period of greater than or equal to 3 years in patients with acute anterior myocardial infarction. It improves regional myocardial function within the infarct zone as well as in remote areas. In patients with acute inferior myocardial infarction, benefit from intravenous streptokinase is of only minor degree.