Nitric oxide (NO) is a highly reactive, ubiquitous respiratory tract product with numerous biological activities. After examining the methodology of the measurement of NO in the exhaled breath, we found that chronic cigarette smoking (n=74, 40 female) lowered exhaled NO, while acute smoking (n=24, 13 female) increased exhaled NO. Since these effects may have related to the chemical reactivity of NO, we studied the effect of oxidant (nitrogen dioxide), antioxidant (ascorbic acid), and D-arginine exposure on exhaled NO. While nitrogen dioxide exposure (n=10, 7 female, 1.5 ppm for 20 minutes) lowered exhaled NO between 1 and 3 hours after exposure, ascorbic acid exposure (n=20, 14 female, 1g daily for 2 weeks) had no effect. D-arginine exposure (n=8, 7 female, 2.5g) increased exhaled NO, suggesting that NO may be formed non-enzymatically from arginine. Finally, the nasal exchange dynamics of NO were studied. NO release was a positive function of luminal gas flow due to a change in mucosal equilibrium. A mathematical model allowed the determination of the nasal mucosal NO concentration and diffusing capacity. In summary, the chemical reactivity of NO may affect biological activity. The human nose provides a convenient source of NO producing mucosa for further in vivo study.