We studied modulation of release of nitric oxide (NO) into nasal passages by physical characteristics (airflow, temperature, humidity) or gases (oxygen, carbon dioxide) in nasal air of humans. Each characteristic or gas in nasal air was changed during voluntary soft palate elevation (to isolate nasal passages). Increasing airflow through the nose caused incremental increases in NO release from 211+/-23 nl/(min x m(-2)) at 1 L/min to 312+/-40 nl/(min x m(-2)) at 22 L/min (P<0.001, n = 6). Decreased humidity (dry airflow, 1-22 L/min) reduced NO release only at the highest airflow rate. Changing temperature (range 46 to 0 degrees C) had no effect on NO release. Hypoxia (below 4% O2) rapidly and reversibly decreased NO release (200+/-40 nl/(min x m(-2)) at 21% O2 versus 99+/-17 nl/(min x m(-2)) at 0% O2 for 3 min, (P<0.001, n = 5). Carbon dioxide (5%) reduced NO release slightly. We conclude that airflow, reduced humidity, carbon dioxide concentration, and oxygen concentration modulate NO release into nasal passages.