Fibronectin is a major adhesive and opsonic glycoprotein found in plasma and tissues. Because this molecule appears to mediate a number of interactions between cells and extracellular matrix, and because the interstitial lung disease are characterized by marked derangements of the pulmonary extracellular matrix, we evaluated fibronectin in the lower respiratory tract in patients with these disorders. Fibronectin could be detected in the bronchoalveolar lavage fluid of normals (11/11), as well as those with noninterstitial lung diseases (18/18), idiopathic pulmonary fibrosis (21/21), sarcoidosis (20/20), and other interstitial lung diseases (22/22). Compared with normal and those with noninterstitial lung disease, the levels in bronchoalveolar lavage of patients with interstitial disease were significantly higher (P less than 0.01), all comparisons). This was true only for bronchoalveolar lavage fibronectin; plasma levels were similar in all study groups (P greater than 0.2, all comparisons). The lavage fluid fibronectin was intact antigenically and retained collagen binding capability, although in some cases of interstitial disease, the presence of lower molecular weight fragments suggested some degradation. Thus, fibronectin is a normal constituent of the epithelial fluid of the lower respiratory tract and is present in increased amounts in a significant number of individuals with interstitial lung disease.