BACKGROUND: The expression and localization of transforming growth factor-beta (TGF-β) pathway proteins in different compartments of the lower airways of stable COPD patients is unclear. OBJECTIVE: To determine TGF-β pathway protein expression in patients with stable COPD. METHODS: The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lung of patients with stable COPD (n=44), control smokers with normal lung function (n=24) and control non-smoking subjects (n=11) using immunohistochemistry. RESULTS: TGF-β1, TGF-β3 and CCN2 expression were significantly decreased in the bronchiolar epithelium, with TGF-β1 also decreased in alveolar macrophages, of stable COPD patients compared to control smokers with normal lung function. TGF-β3 expression was increased in the bronchial lamina propria of both control smokers with normal lung function and mild/moderate stable COPD compared to control non-smokers and correlated significantly with pack-years. However, TGF-β3+ cells decreased in severe/very severe COPD compared to control smokers. LTBP-1 expression was increased in the bronchial lamina propria in stable COPD of all severities compared with control smokers with normal lung function. BAMBI expression in the bronchial mucosa was significantly increased in stable COPD of all severities compared to control subjects. No other significant differences were observed between groups for all the other molecules studied either in the bronchial mucosa and peripheral lung. CONCLUSION: Expression of TGF-βs and their regulatory proteins is distinct within different lower airway compartments in stable COPD. Selective reduction in TGF-β1 and enhanced BAMBI expression may be associated with the increase in autoimmunity in COPD.