It is known that smoking affects the development and maintenance of certain types of granulomatous lung diseases. To explore this mechanism(s), we measured tumor necrosis factor (TNF)-alpha concentrations in the culture supernatants of lipopolysaccharide (LPS)-stimulated alveolar macrophages (AMs) in 13 healthy nonsmokers, 13 healthy smokers, 13 nonsmoking sarcoid patients, and 16 smoking sarcoid patients. We found that the capacity of smokers' AMs to release TNF-alpha was significantly decreased both in the normal and sarcoid groups. We also confirmed the previous observation that there was an exaggerated TNF release in patients with pulmonary sarcoidosis. These results indicate a significant role of TNF-alpha in the pathogenetic mechanisms of pulmonary sarcoidosis and suggest the possible involvement of TNF in the mechanisms by which smoking modulates local immune phenomena.