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Early studies in experimental animals and in humans indicated the need to examine the feasibility of infarct size reduction by the early treatment of patients recruited to well-designed clinical trials. The extensive experience with β-adrenoceptor blockers and the comparatively recent data generated with the use of calcium antagonists in patients with acute myocardial infarction are reviewed. Early intravenous administration of β-adrenoceptor blockers in suitable patients appears to produce genuine infarct size reduction (approximately 20%) compared with controls, whereas calcium channel antagonists have failed to demonstrate such an effect. Possible mechanisms for these findings are discussed.