Chronic obstructive pulmonary disease (COPD) is characterized by inflammation of the respiratory tract in which macrophages are the predominant inflammatory cell and for which the efficacy of treatment with corticosteroids is controversial. We investigated the effect of dexamethasone on basal and interleukin (IL)-1beta or cigarette smoke media (CSM)-stimulated release of IL-8 and granulocyte macrophage-colony stimulating factor (GM-CSF) by bronchoalveolar lavage macrophages from cigarette smokers and patients with COPD (n = 15). Basal release of IL-8 was approximately fivefold greater in patients with COPD than smokers, whereas GM-CSF was similar for each group. IL-1beta and CSM increased IL-8 and GM-CSF release by macrophages from both smokers and patients with COPD. Dexamethasone did not inhibit basal or stimulated IL-8 release from macrophages from patients with COPD but inhibited release in smokers. In contrast, basal and IL-1beta-stimulated GM-CSF release, but not CSM-stimulated release, was inhibited by dexamethasone. We conclude that the lack of efficacy of corticosteroids in COPD might be due to the relative steroid insensitivity of macrophages in the respiratory tract.