Smokers have been found to have low exhaled nitric oxide (NO) levels. The aim of the present study was to investigate where in the respiratory system the decrease in NO occurs, and whether this decrease was affected by smoking cessation. Measurements of exhaled NO were carried out in smokers (n=20) and non-smoking control subjects (n=30). In nine of the smokers, exhaled NO was analysed 1, 2 and 4 weeks after smoking cessation. The level of exhaled NO at a flow rate of 0.1 litre/s was significantly lower in smokers (4+/-2 p.p.b.) than in non-smokers (7+/-5 p.p.b.; P=0.007). A calculation of the contributions from different areas of the lung showed that the NO flux from the airways was significantly lower (14+/-10 compared with 36+/-26 nl/min; P=0.0001) and the alveolar fraction was significantly higher (2.1+/-0.8 compared with 1.5+/-0.9 p.p.b.; P=0.006) in smokers than in non-smokers. Nine smoking subjects refrained from smoking for 4 weeks, and this resulted in increased NO flux from the airways of 28+/-17 nl/min, which was no longer significantly different from controls. In conclusion, endogenous production of NO in the airways is decreased in smokers, but can be restored to normal values by 4 weeks after cessation of smoking. Smokers have an increased alveolar fraction of NO, and this might be a diagnostic sign of lung damage. Thus NO monitoring can be used to indicate improvements when a smoker decides to stop smoking.