The effect of acute coronary ligation on infarct size was studied in (1) ten acute control dogs, which were non-denervated, (2) in six acutely denervated dogs in which the heart was denervated immediately prior to coronary ligation and in which intra-cardiac reflexes were pharmacologically blocked, (3) in seven chronically denervated dogs in which intrapericardial nerves were cut 2 weeks prior to ligation, and (4) in four dogs which were sham-operated 2 weeks prior to ligation. Infarct size was determined using a nitro blue tetrazolium stain for dehydrogenase activity. Infarct sizes in acute controls, acutely denervated, chronically denervated, and sham-operated hearts were 20.1, 15.0, 3.8, and 21.0 per cent of left ventricular weight, respectively. Infarct sizes in acutely and chronically denervated hearts were significantly less than in acute controls (P less than 0.05). In further studies the fluorescent stain thioflavin S was used to demonstrate that perfusion of myocardium distal to the ligation was substantially greater in chronically denervated hearts than in acute controls.