We studied the effects of regional epicardial application of phenol on autonomic neural control of electrophysiological characteristics of the anterior left ventricle. In eight open-chest dogs, we applied a thin line of 88± phenol on the perimeter encircling a multipolar electrode and measured the effective refractory period (ERP) and recorded electrograms in phenol-encircled and untreated areas. Before phenol was applied, sympathetic nerve stimulation shortened ERP in all areas: percent change (Δ) ⩾ 12. Phenol application to an area with a radius of 1-2 cm prevented ERP shortening in encircled epicardium during sympathetic stimulation, ±Δ = 0.9 ± 0.8 (SEM), and attenuated ERP shortening in underlying endocardium, ±Δ = 2.5 ± 1.6, compared to ERP shortening in untreated areas, ±Δ = 10 ± 1. A subsequent phenol application to an area with a radius of 2-3 cm prevented ERP shortening during sympathetic stimulation in both encircled epicardium and underlying endocardium. Phenol did not alter electrograms, activation times, or ERP shortening produced by norepinephrine infusion; these data suggest that electrophysiological characteristics of ventricular muscle encircled by phenol were unchanged apart from effects of withdrawal of sympathetic neural influence. To support these functional data, norepinephrine content measured in phenol-treated epicardium and endocardium of three dogs was 7 and 21±, respectively, of the norepinephrine content of untreated areas. In eight additional dogs, vagus nerve stimulation during norepinephrine infusion prolonged ERP by 3-5 msec both before and after phenol encircling an area with a radius of 2-3 cm. In these dogs, phenol did prevent ERP shortening during sympathetic nerve stimulation. We conclude that epicardial phenol interrupts sympathetic neural influences to both epicardial and endocardial sites without impairing responses either to intravenous norepinephrine or to vagus nerve stimulation.Circ Res 47: 33-40, 1980