Analysis of exhaled nitric oxide (NO) has become an accepted complementary tool in the management of inflammatory airway diseases. Previous studies have demonstrated reduced exhaled NO at altitude and ascribed their findings to hypoxia. We studied exhaled NO partial pressures (Pe(NO)) in eight healthy subjects at reduced ambient pressure down to 540 hPa (equivalent to 5000 m altitude) and at sea level, with equivalently hypoxic breathing gases (down to 11.3% O2 in N2). Pe(NO) readings were corrected for gas density effects on the instrument performance. Sea level control values for Pe(NO) at an exhaled flow of 50 mls(-1) averaged 2.4 mPa and were virtually unchanged with normobaric hypoxia down to an inspired P(O)(2) of 10.7 kPa. With the same degree of hypoxia, hypobaric Pe(NO) was 1.4 mPa. The reduction in hypobaric Pe(NO) of up to 33+/-16% (mean+/-SD) in comparison to normobaric Pe(NO), is likely to have been caused by enhanced axial back diffusion of NO because of the reduced gas density and an associated increased alveolar NO uptake to the blood.