We evaluated the completeness and extent of regional sympathetic denervation of the left ventricle after epicardial painting with phenol in anesthetized dogs. In a region encircled by phenol, the effect of electrical stimulation of efferent sympathetic fibers on myocardial contractility and coronary vascular resistance was completely abolished within 30 min. Denervation extended to untreated regions innervated by sympathetic fibers crossing the phenol line. For at least 4 h after phenol application, intravenous infusion of isoproterenol or coronary arterial infusion of tyramine increased myocardial contractility in the denervated region; norepinephrine content and neurotransmitter uptake were normal, indicating that nerve terminals, postjunctional receptors, and myocardium remained functional. However, after 3-14 days, tissue catecholamine content and transmitter uptake in the encircled area were markedly reduced. The results suggest that careful evaluation is necessary in selecting a fully innervated control region in studies employing regional sympathetic denervation with phenol.