The mechanism by which early intervention with beta-blockers reduces mortality in acute myocardial infarction is unclear. Therefore the effects of intravenous, followed by oral, metoprolol on indices of infarct size were studied in a double-blind fashion with a median delay of 6.75 hours from onset of symptoms. In 129 patients peak enzyme release and QRS score on the electrocardiogram were assessed, while myocardial perfusion score on thallium-201 scintigraphy was studied in 45 patients. There was a close correlation between all the indices of infarct size. While the correlation coefficients did not appear to be influenced by metoprolol treatment, the slope of the regression was affected. Peak aspartate aminotransferase and lactic dehydrogenase were lower by 11 and 7%, respectively, in the metoprolol-treated group, but no reduction was noted in QRS score or in thallium-201 perfusion defect size in the actively treated group. Thus, it seems likely that early intervention with metoprolol in acute myocardial infarction reduces mortality, not by limiting infarct size, but by some other mechanism.