We studied the possibility that intravenous nitroglycerin may produce heparin resistance both in vitro and prospectively in a group of 10 patients following coronary angioplasty. Nitroglycerin in physiologic to pharmacologic concentrations (41-250 micrograms/ml) did not produce heparin resistance in vitro as measured by activated partial thromboplastin time and thrombin time. The maximum reduction in activated partial thromboplastin time was 7%. In patient studies, the activated partial thromboplastin time at baseline on heparin alone (93 + 22 s) was not significantly different (p = 0.61) from activated partial thromboplastin measured upon addition of nitroglycerin (94 +/- 27 s) or 30 min following cessation of the nitroglycerin infusion while continuing the same dose of heparin (91 +/- 24 s). We conclude that intravenous nitroglycerin does not induce heparin resistance in vitro or in patients during short-term administration.