The present study was designed to examine the safety and efficacy of titrating a nitroglycerin infusion to a fixed hemodynamic endpoint as initial therapy for patients admitted to a coronary care unit for medically refractory unstable angina, and to test the hypothesis that patients, responding to the addition of intravenous (i.v.) nitroglycerin to their previous antianginal regimen, could be crossed over to nitroglycerin administered by a new transdermal delivery system. In 9 patients the nitroglycerin infusion titrated upward at 3- to 10-minute intervals until a 10% reduction in mean arterial pressure was achieved. This titration schedule and hemodynamic endpoint proved safe and effective for controlling episodes of chest pain at rest in all 9 patients. Subsequently, this treatment strategy was tested in 17 consecutive patients with unstable angina treated in our coronary care unit during a 1-month period. In 10 of 15 successfully treated patients ischemia was the cause of chest pain as documented by cardiac catheterization. No change was made in antianginal or vasoactive drugs during the period of i.v. nitroglycerin administration or during crossover to transdermal therapy. In this well defined subgroup of patients with unstable angina, nitroglycerin infusion decreased the mean arterial pressure from 101 +/- 18 to 87 +/- 11 mm Hg (mean +/- standard deviation), using an infusion rate of 84 +/- 74 micrograms/min (range 10 to 200). The mean duration of i.v. therapy was 36 +/- 12 hours.(ABSTRACT TRUNCATED AT 250 WORDS)