Thirty-five patients who had angina at rest that was unresponsive to standard therapy comprised of oral or topical nitrates and beta-blocking drugs were treated with a continuous infusion of intravenous nitroglycerin (IVNTG). The infusion was started at 10 micrograms/min and increased by 10 micrograms/min increments every 5 minutes until an infusion rate of 50 micrograms/min was reached. After each episode of rest angina, the infusion was increased by 50 micrograms/min in the same stepwise manner. Data from a 24-hour baseline control period were compared with those from a 24-hour IVNTG endpoint period at which time the highest IVNTG infusion rate was administered. The average IVNTG infusion rate was 140 +/- 15 micrograms/min. With IVNTG therapy, the number of episodes of angina at rest decreased from 3.5 +/- 0.4 to 0.3 +/- 0.1, sublingual nitroglycerin use decreased from 1.9 +/- 0.3 to 0.4 +/- 0.1 mg/day, and morphine sulfate administration decreased from 5.5 +/- 1.3 to 0.4 +/- 0.2 mg/day (all p less than 0.001). When each patient's response on the endpoint day was analyzed, 25 were defined as complete (no rest angina), 8 as partial (greater than 50% decrease in the number of episodes/day from control values), and 2 as nonresponders. No significant drug-induced adverse effects occurred. IVNTG appears to be effective therapy for angina at rest refractory to standard oral and topical medications.