The effect of metoprolol on indices of infarct size and left ventricular function was compared with that of placebo in a double-blind randomized trial in patients with definite or suspected acute myocardial infarction. Intravenous metoprolol (15 mg) or placebo was given within 24 h of the onset of symptoms, and oral treatment (200 mg daily) was continued for 15 days. Thirty-five patients received metoprolol and 34 patients placebo. The mean (+/- SD) of maximal creatinine phosphokinase (CK)-MB activities was 142 +/- 110 IU/l in the placebo group and 74 +/- 72 IU/l in the metoprolol group (p less than 0.001). The ECG QRS score at discharge from hospital was 5.22 +/- 4.47 and 4.61 +/- 3.06 (NS), respectively. Global left ventricular ejection fraction at rest was 44 +/- 14 and 51 +/- 15% (p = 0.054), respectively, and no change occurred in either group from rest to peak exercise. Ventricular fibrillation occurred in 1 placebo patient during the first day in hospital and in 1 metoprolol patient on the 14th day. Holter monitoring revealed no significant difference in the occurrence of ventricular arrhythmias during the first 24 h. Smaller enzyme release and higher ejection fraction suggest myocardial protection by early metoprolol treatment in acute myocardial infarction.