To evaluate the incidence of air-blood barrier lesions in the course of chronic interstitial lung diseases, we studied by electron microscopy open lung biopsy specimens from patients with sarcoidosis or chronic hypersensitivity pneumonitis, and compared the distribution of ultrastructural air-blood barrier lesions (including swelling or destruction of epithelial and endothelial cells, type II cell hyperplasia, and basement membrane disruption) with the type of histopathologic abnormalities present (including inflammation, inflammation and fibrosis, or fibrosis alone). Ultrastructural lesions of the air-blood barrier were frequently observed in sarcoidosis as well as hypersensitivity pneumonitis. Their nature and distribution were highly dependent on the histologic pattern of lung tissue in which they were present: epithelial and/or endothelial injury was more frequently observed in inflammatory areas (90 to 100% of all lung specimens displaying inflammation alone), whereas type II cell hyperplasia was mainly identified in fibrotic tissues (83 to 100% of all lung specimens displaying fibrosis alone). Strikingly, in lung tissue considered as normal by light microscopy, air-blood barrier was frequently found to be damaged (50 to 62% of apparently normal lung specimens), suggesting that alveolar lesions may constitute an early phenomenon in the course of pulmonary inflammatory processes. The air-blood barrier alterations observed in this study may provide an anatomic basis for the modifications of alveolar permeability described in pulmonary sarcoidosis and hypersensitivity pneumonitis.