The effect of total cardiac denervation upon the electrophysiology of infarcted canine myocardium was studied at both organ and cellular levels. Fifteen dogs underwent coronary ligation to produce an infarct at the apex of the left ventricle (Group 1, n = 15). A second group of dogs (Group 2, n = 14) underwent total intrapericardial denervation with subsequent infarct 15.0 +/- 0.3 (mean +/- SEM) days later. All animals had bipolar epicardial pacing electrodes placed on the right ventricle and the infarct border zone of the left ventricle. Strength-interval curves were performed one or two times per week in conscious animals to assess cardiac excitability. Animals were sacrificed 18.1 +/- 0.5 days following infarct and histologic studies were performed to determine infarct size. Standard microelectrode techniques were also utilized to determine cellular parameters. Denervation was found to lengthen the absolute refractory period and prevent increases in the relative refractory period which were observed in innervated animals following infarct. Isolated tissue data including measurements of maximal rate of depolarization, mean diastolic potential, action potential amplitude, action potential duration at 50% repolarization, and effective refractory period indicated that denervation protects against cellular deterioration and improves electrophysiologic cellular characteristics. These studies suggest that under conditions of myocardial ischemia, denervation produces an electrically more stable myocardium which is less excitable and probably less vulnerable to lethal arrhythmias.