We examined the effects of endogenous nitric oxide synthase (NOS) inhibition on pulmonary hemodynamics in awake sheep living at low and high altitudes to evaluate the role of NO in adaptation to an hypoxic environment. Unanaesthetized male sheep in three places--Matsumoto, Japan (680 m above sea level), Xing, China (2300 m) and Maxin, China (3750 m)--were prepared for measurements of pulmonary artery (Ppa) and pulmonary vascular resistance (PVR) before and after the NOS inhibition. The non-selective NOS inhibitor, Nw-nitro-l-argine (NLA, 20 mg/kg) was used. Baseline Ppa became elevated with an increase in altitude. After NLA administration, PVR significantly increased in animals of all groups. However, the increase in PVR after NLA in tibetan sheep at 3750 m was significantly higher than those in other groups. We conclude that augmented endogenous NO production may contribute to regulating the pulmonary vascular tone in tibetan sheep (3750 m) adapted to high altitude.