Quantitation of exhaled nitric oxide (NO) and carbon monoxide (CO) has been proposed to noninvasively measure markers of airway inflammation. We hypothesized that exhaled carbon monoxide (CO) is increased in individuals with alpha-1-antitrypsin (₁-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 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. Nitric oxide 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. Demonstrating lower than normal CO and NO levels may be useful as an additional noninvasive method to evaluate for ₁-AT deficiency in individuals with severe, early onset obstructive lung disease.