In this investigation, tenascin (Tn) expression was studied in 51 cases of different types of fibrotic lung disorders originating for years 1981 to 1995. Our aim was to test if accumulation of Tn at the site of lung injury in usual interstitial pneumonia (UIP) could correlate with the prognosis. Lung biopsies taken from 28 patients with UIP, six with desquamative interstitial pneumonia (DIP), six with sarcoidosis, five with extrinsic allergic bronchioloalveolitis, five with bronchiolitis obliterans organizing pneumonia (BOOP), and one with nonspecific interstitial pneumonia were studied for the expression of Tn by using an immunohistochemical technique. In addition to Tn immunohistochemistry, selected cases were also studied by immunoelectron microscopy and Western blotting. For prognostic studies in UIP the clinical follow-up information was obtained from the patient records. The expression of Tn was increased in each type of fibrosis, especially in UIP. In immunoelectron microscopy the most prominent labeling in UIP was found in association with collagen fibers and within the type 2 pneumocytes. Every studied case of UIP showed reactivity for a polypeptide of M(r) approximately equal to 200,000 by Western blotting. In patients with UIP, increased Tn expression, especially under metaplastic bronchiolar-type epithelium, was associated with a shortened survival time. Immunoelectron microscopic findings support the idea that Tn in UIP is synthesized by the regenerating epithelial rather than interstitial cells in response to pulmonary interstitial inflammation.