Vascular selectivity of lacidipine, a new potent and long-acting coronary vasodilator, was evaluated by a comparison with its negative inotropic, chronotropic, and dromotropic effects in canine isolated, blood-perfused heart preparations. The drug was injected into each nutrient artery in a bolus fashion. In the papillary muscle preparation, the dose causing a 50% increase in blood flow through the anterior septal artery was 0.23 micrograms (mean of five experiments) and the time required for return to half maximum at this dose was 15.0 min even with a bolus injection. Meanwhile, the dose causing a 50% decrease in developed tension of the papillary muscle was 4.6 micrograms. The dose producing a 15% decrease in sinoatrial rate in the sinoatrial node preparation was 8.4 micrograms (n = 5) and that causing a 50% increase in atrio-His interval in the atrioventricular node preparation was 6.8 micrograms (n = 7). These results indicate that the vascular selectivity of lacidipine is markedly high not only against ventricular contractility but also against sinoatrial node automaticity and atrioventricular nodal conduction. The high lipophilicity of lacidipine might be related, at least in part, to its high vascular selectivity, which was equieffective against all the intracardiac variables measured.