The mechanism of action of 2-nicotinamidoethyl nitrate (SG-75) was studied using arterially blood-perfused papillary muscle preparations of the dog. All drugs were administered intra-arterially. SG-75 shortened the effective refractory period (ERP) and decreased the rate of automaticity and developed tension of the papillary muscle, but verapamil failed to change the ERP despite a decrease in the developed tension. SG-75 in extremely high doses induced ventricular fibrillation. Methacholine produced decreases in the rate of automaticity and developed tension, and the actions were abolished by atropine. The SG-75-induced decreases in 2 parameters were not modified by atropine. The cardiac action of SG-75 differs from that of Ca-antagonistic vasodilators and apparently the basic mechanism of action of SG-75 involves an increase in K conductance in the membrane of cardiac muscle, without mediation through muscarinic receptors.