Quantitations of exhaled nitric oxide (NO) and carbon monoxide (CO) have been proposed as noninvasive markers of airway inflammation. We hypothesized that exhaled CO is increased in individuals with ₁-antitrypsin (AT) deficiency, who have lung inflammation and injury related to oxidative and proteolytic processes. Nineteen individuals with ₁-AT deficiency, 22 healthy controls, and 12 patients with non-₁-AT-deficient chronic obstructive pulmonary disease (COPD) had NO, CO, CO₂, and O₂ measured in exhaled breath. Individuals with ₁-AT deficiency had lower levels of NO and CO than control or COPD individuals. ₁-AT-deficient and COPD patients had lower exhaled CO₂ than controls, although only ₁-AT-deficient patients had higher exhaled O₂ than healthy controls. NO was correlated inversely with exhaled O₂ and directly with exhaled CO₂, supporting a role for NO in regulation of gas exchange. Exhaled gases were not significantly related to corticosteroid use or lung function. Demonstration of lower than normal CO and NO levels may be useful as an additional noninvasive method to evaluate ₁-AT deficiency in individuals with a severe, early onset of obstructive lung disease.