Cigarette smoking is associated with an increased risk of respiratory tract infections, chronic airway disease, and cardiovascular diseases, all of which may be modulated by endogenous nitric oxide (NO). We have investigated whether cigarette smoking reduces the production of endogenous NO. We compared exhalations of 41 current cigarette smokers with normal lung function and 73 age-matched non-smoking controls. Peak exhaled NO levels were measured by a modified chemiluminescence analyzer. The effects of inhaling a single cigarette in smokers were also measured. In control subjects we also measured the effects of inhalation of NO itself and carbon monoxide, both constituents of tobacco smoke. Peak exhaled NO concentrations were significantly reduced in smokers (42 +/- 3.9 compared with 88 +/- 2.7 parts per billion in nonsmokers, p < 0.01), with a significant relation between the exhaled NO and cigarette consumption (r = 0.77, p < 0.001). Smoking a single cigarette also significantly (p < 0.02), but transiently, reduced exhaled NO. Inhalation of carbon monoxide and NO had no effect on exhaled NO in normal subjects. Cigarette smoking decreased exhaled NO, suggesting that it may inhibit the enzyme NO synthase. Since endogenous NO is important in defending the respiratory tract against infection, in counteracting bronchoconstriction and vasoconstriction, and in inhibiting platelet aggregation, this effect may contribute to the increased risks of chronic respiratory and cardiovascular disease in cigarette smokers.