We evaluated the effects of sublingual nitroglycerin on indices of regional coronary flow and coronary resistance (CR) in 12 selected patients with coronary artery disease (CAD) and eight with normal coronary arteries (NCA), using continuous thermodilution. Resting total left ventricular flow, reflected by coronary sinus flow (CSF), and anterior regional flow, reflected by great cardiac vein flow (GCVF), in NCA and CAD patient groups, were similar. However, in a subgroup of six patients, with CAD limited to the anterior descending artery, GCVF was lower and anterior regional CR (CRANT) higher than the NCA subjects. Nitroglycerin reduced the systolic pressure-heart rate product similarly in both patient groups. CSF and GCVF in NCA subjects declined 15% and 17%, respectively, as total CR (CRT) and CRANT increased. In the CAD subgroup, consisting of patients with CAD limited to the anterior descending, GCVF increased 48% as CRANT declined 50%, and CSF was unchanged. In the other CAD subgroup of patients with CAD in the right and/or circumflex arteries, GCVF declined 32% and CRANT increased 46% as CSF was minimally increased. These data imply that sublingual nitroglycerin reduces both CSF and GCVF in NCA patients as oxygen demands decrease. In certain CAD patients, however, nitroglycerin alters regional coronary venous blood flow, suggesting a redistribution of flow from normally perfused to hypoperfused regions.