Oxidative stress caused by airway inflammation is increased in chronic obstructive pulmonary disease (COPD) and may account for the progressive deterioration of structure and function of the respiratory tract observed in this disease. Antioxidant defences of the respiratory tract may be overwhelmed by the oxidant burden in COPD and possibly restored with antioxidant therapy. The level of hydrogen peroxide (H(2)O(2)) concentration in exhaled air condensate (EAC) is a valuable tool for assessing and monitoring oxidative stress. This study aimed to verify the effect of 2-month oral N-acetylcysteine (NAC) treatment compared to placebo on the H(2)O(2) content in EAC of 55 clinically stable COPD patients (48 males), mean age 65.93+/-9.3 years. After clinical examination, pulmonary function tests, and collection of EAC for the basal (T0) assay of H(2)O(2), patients were randomly allocated to group A (usual therapy plus oral NAC 600 mg b.i.d. for 2 months) or group B (usual therapy plus placebo b.i.d. for 2 months). H(2)O(2) assay in EAC was repeated at 15 (T15), 30 (T30), and 60 (T60) days after the start of therapy in each group. All patients were non-smokers or ex smokers for at least 5 years and the two groups were comparable in terms of demographic, respiratory function, and EAC data at baseline. The H(2)O(2) level in EAC of group A was significantly decreased at T15 (1.00+/-0.38 SD microM; p=0.003), T30 (0.91+/-0.44 microM; p=0.007), and T60 (0.83+/-0.41 microM; p=0.000) compared to T0 (1.28+/-0.61 microM). No significant decrease in H(2)O(2) of group B was found at any time point. We conclude that oral NAC 600 mg b.i.d. for 2 months rapidly reduces the oxidant burden in airways of stable COPD patients.