Background. There are a number of evidences suggesting that lung perfusion distribution is under an active regulation and determined by several factors in addition to gravity. In this work we hypothesised that autoinhalation of nitric oxide (NO), produced in the human nasal airways, may be one important factor regulating human lung perfusion distribution in the upright position. Methods. In fifteen healthy volunteers we used single photon emission computed tomography technique and two tracers ( ^99mTc and ^113m In) labelled with human macro aggregated albumin, to assess pulmonary blood flow distribution. In the sitting upright position the subjects first breathed NO free air through the mouth, followed by administration of the first tracer. The subjects then switched to either nasal breathing or oral breathing with addition of exogenous NO-enriched air, followed by administration of the second tracer. Results. Compared to oral breathing, nasal breathing induces a blood flow redistribution of about 4% of the total perfusion in the caudal to cranial and dorsal to ventral directions. For low perfused lung regions like the apical, this represents a net increase of 24% in blood flow. Similar effects were obtained with addition of exogenous NO during oral breathing, indicating that NO and not the breathing condition is responsible for the blood flow redistribution. Conclusions. These results provide evidence that autoinhalation of endogenous NO from the nasal airways may ameliorate the influence of gravity on pulmonary blood flow distribution in the upright position. The presence of nasal NO only in humans and higher primates suggest that it may be an important part of the adaptation to bipedalism.