The results of the propranolol limb of the Multicenter Investigation of the Limitation of Infarct Size are reviewed. A total of 269 patients, who presented with symptoms and electrocardiographic signs suggesting acute myocardial infarction were randomized to acute intravenous and subsequent oral therapy with propranolol (n = 134) or placebo (n = 135). Eligibility for acute beta-blocker therapy was determined on the basis of readily available, noninvasive tests. Therapy was started at an average time of 8.5 hours after onset of symptoms. The full induction dose of intravenous propranolol (0.1 mg/kg) was tolerated by 90% of treated patients, and oral maintenance therapy was being continued in 82% of treated patients on the second hospital day. There was a significant reduction in heart rate throughout maintenance therapy with propranolol, which continued through the tenth hospital day. There was no significant difference in the incidence of congestive heart failure between propranolol- and placebo-treated groups. There was also no significant difference between the 2 groups in infarct size estimated by measurement of serum CK-MB, planimetry of infarct area on technetium pyrophosphate myocardial scintigrams or R-wave measurements in patients with transmural anterior and inferior infarcts. There was no significant difference in mortality between the 2 groups during an average of 36 months' follow-up. Although propranolol can be administered safely to patients with acute myocardial infarction who are selected on the basis of simple clinical criteria, there is no evidence of reduction of infarct size when beta blockade is begun 8.5 hours after the onset of symptoms.