The dose of intravenously administered nitroglycerin (IV NTG) used to control ischemic chest pain usually is limited by hypotension from decreased preload. Herein we describe 2 patients who tolerated IV NTG without hemodynamic compromise but in whom severe impairment of blood oxygen content developed from methemoglobinemia noted during coronary bypass surgery. Methemoglobinemia must be suspected if chocolate-brown blood is encountered despite a normal arterial oxygen tension and calculated oxygen saturation. Before a methemoglobin level is available, the extent of hypoxemia can be determined by an oximetric oxygen saturation and therapy begun with intravenous administration of methylene blue. These case reports focus attention on the potential deleterious effects of undetected hypoxemia from methemoglobinemia in patients being stabilized with high-dose IV NTG for urgent cardiac surgery.