The concentrations of endogenous nitric oxide (NO) and CO2 were measured in exhaled air from healthy humans. During a single exhalation, NO concentrations peaked when the CO2 level reached its plateau. However, whereas CO2 levels remained at a plateau throughout the exhalation, NO concentrations declined after having peaked. After breathholding (5 to 60 s) NO peaked at a higher level than during normal breathing. Nitric oxide concentrations in exhaled air decreased during physical exercise (50 to 100 W). However, taking the increased ventilatory minute volume into account, excretion of NO markedly increased during exercise. The data are compatible with the hypothesis that the NO detected in exhaled air is formed preferentially in the terminal and respiratory bronchioles, and they suggest increased production of NO into exhaled air during exercise and during hyperventilation at rest.