The effects of nifedipine, 20 micrograms/kg, iv, and nitroglycerin, 25 micrograms/kg, iv, were compared in conscious dogs, instrumented for instantaneous and continuous measurements of coronary arterial and left ventricular (LV) diameters, arterial and LV pressures, coronary blood flow, and cardiac output. The two drugs were administered to reduce arterial pressure initially by similar amounts, by approximately 30 mm Hg. The maximal increases in large coronary arterial dimensions occurred 2-4 minutes after the initial peak reductions in arterial pressure and increases in coronary blood flow. The maximal increase in large coronary arterial cross-sectional area with nifedipine (28 +/- 2.9%) and nitroglycerin (33 +/- 5.3%) were similar. At this time, nifedipine increased coronary blood flow (114 +/- 20%) and reduced late diastolic coronary vascular resistance (-61 +/- 3.1%), whereas nitroglycerin reduced coronary blood flow (-14 +/- 1.7%) and increased late diastolic coronary vascular resistance (15 +/- 6.6%). During the time of peak large coronary arterial dilation, nifedipine reduced mean arterial pressure (-13 +/- 2.1%) and total peripheral resistance (-30 +/- 2.6%), whereas, with nitroglycerin, arterial pressure was not different from control and total peripheral resistance was significantly increased (13 +/- 1.8%). At this time, LV end-diastolic diameter was reduced with nitroglycerin (-5.6 +/- 0.4%) but unaffected by nifedipine. Thus, in the conscious dog, nitroglycerin and nifedipine induced similar effects on large coronary arteries but differing effects on resistance coronary and peripheral vessels as well as preload. Nifedipine, in contrast to nitroglycerin, induced sustained vasodilation of both coronary resistance vessels and peripheral arterioles, whereas nitroglycerin, but not nifedipine, reduced preload.