Twenty patients with refractory rest angina pectoris were treated with intravenously (IV) administered nitroglycerin (mean dosage, 72.4 micrograms/min; range, 15 to 226 micrograms/min). There was a considerable reduction or abolition in the number of ischemic episodes in 85% of patients without overall substantial changes in heart rate, mean arterial BP, pulmonary capillary wedge pressure (PCWP), and pulmonary arterial mean pressure. However, those patients with an initial PCWP of more than 12 mm Hg or a systolic pressure of more than 130 mm Hg had a substantial reduction in PCWP and systolic BP following IV nitroglycerin. We conclude that IV nitroglycerin may relieve rest angina by different pathophysiologic mechanisms. In some patients, IV nitroglycerin favorably altered the hemodynamic determinants of myocardial oxygen consumption. In others, however, no change in these determinants occurred, suggesting a direct effect on the coronary circulation.