The threshold for ventricular fibrillation induced by a 200 msec train of pulses was measured during a control period and during an intravenous infusion of nitroglycerin in 14 nonischemic open chest dogs. Infusion of nitroglycerin in doses sufficient to reduce mean arterial blood pressure an average of 17 mm Hg was associated with a rise in ventricular fibrillation threshold from a control value of 24 +/- 3 (mean +/- 1 standard error of the mean) to 41 +/- 6 milliamperes (P less than 0.001). In a subgroup of six animals simultaneous infusions of nitroglycerin and phenylephrine abolished the hypotensive effect of nitroglycerin but did not significantly alter the rise in ventricular fibrillation threshold observed with nitroglycerin infusion alone. In five other animals mean arterial blood pressure was similarly reduced an average of 17 mm Hg by venous hemorrhage, but was associated with a lowering than a rise in ventricular fibrillation threshold from a prehemorrhage value of 28 +/- 6 to 15 +/- 2 milliamperes, (P less than 0.005). Thus, intravenously administered nitroglycerin raises ventricular fibrillation threshold in nonischemic canine myocardium independent of its hypotensive effects.