Sympathetic innervation of the normal and acutely ischemic myocardium and the effects of regional myocardial sympathetic denervation of the ischemic area on the evolving electrical changes during coronary occlusion were assessed in pigs anesthetized with pentobarbital sodium. The histofluorescence of the adrenergic nerve fibers (glyoxylic acid reaction), which in the normal myocardium were distributed in a diffuse network, decreased slightly after 45 min of occlusion of the left anterior descending (LAD) coronary artery and nearly disappeared after 2 h of ischemia. Topical application of phenol (carbolic acid, 88%) to the coronary arterial wall produced a transmural loss of catecholamine histofluorescence in the distal myocardium supplied by the phenol-treated arterial segment. Mapping of the epicardial direct current (DC) electrograms in sympathetically denervated and in nondenervated sections of the same ischemic area, using three rows of seven cotton-wick electrodes, was performed in eight pigs and validated in eight other nondenervated pigs. During 45 min of LAD occlusion, the denervated area, with respect to the nondenervated region, showed a greater decline in T-Q segment depression after 20 min of ischemia (P less than 0.0001), a lesser degree of S-T segment elevation throughout the study (P less than 0.0001), a delayed development of monophasic potentials (P less than 0.05), a minor degree of S-T segment alternans (P less than 0.0001), and a less marked, but still present, period of transient electrical recovery. Thus acute regional myocardial sympathectomy reduces the magnitude of the local electrical manifestations of acute myocardial ischemia in the in situ pig heart. Also in this model, sympathetic fibers appeared to lose the catecholamine histofluorescence after 2 h of acute ischemia.