As arterial partial pressure of O2 (PaO2) is reduced during systemic hypoxia, right ventricular (RV) work and myocardial O2 consumption (MV̇o2) increase. Mechanisms responsible for maintaining RV O2 demand/supply balance during hypoxia have not been delineated. To address this problem, right coronary (RC) blood flow and RV O2 extraction were measured in nine conscious, instrumented dogs exposed to normobaric hypoxia. Catheters were implanted in the right ventricle for measuring pressure, in the ascending aorta for measuring arterial pressure and for sampling arterial blood, and in an RC vein. A flow transducer was placed around the RC artery. After recovery from surgery, dogs were exposed to hypoxia in a chamber ventilated with N2, and blood samples and hemodynamic data were collected as chamber O2 was reduced progressively to ∼8%. After control measurements were made, the chamber was opened and the dog was allowed to recover. Nω-nitro-l-arginine (l-NNA) was then administered (35 mg/kg, via RV catheter) to inhibit nitric oxide (NO) production, and the hypoxia protocol was repeated. RC blood flow increased during hypoxia due to coronary vasodilation, because RC conductance increased from 0.65 ± 0.05 to 1.32 ± 0.12 ml·min−1·100 g−1. l-NNA blunted the hypoxia-induced increase in RC conductance. RV O2 extraction remained constant at 64 ± 4% as PaO2 was decreased, but after l-NNA, extraction increased to 70 ± 3% during normoxia and then to 78 ± 3% during hypoxia. RV MV̇o2 increased during hypoxia, but after l-NNA, MV̇o2 was lower at any respective PaO2. The relationship between heart rate times RV systolic pressure (rate-pressure product) and RV MV̇o2 was not altered by l-NNA. To account for l-NNA-mediated decreases in RV MV̇o2, O2 demand/supply variables were plotted as functions of MV̇o2. Slope of the conductance-MV̇o2 relationship was depressed by l-NNA ( P = 0.03), whereas the slope of the extraction-MV̇o2 relationship increased ( P = 0.003). In summary, increases in RV MV̇o2 during hypoxia are met normally by increasing RC blood flow. When NO synthesis is blocked, the large RV O2 extraction reserve is mobilized to maintain RV O2 demand/supply balance. We conclude that NO contributes to RC vasodilation during systemic hypoxia.