Fibrin deposition is prominent in the histopathologic features of chronic interstitial lung disease. Human alveolar macrophages can potentially modulate this process because normal macrophages synthesize and express the initial enzymes of both coagulation and fibrinolytic pathways. In the present study, we examined the cell-associated procoagulant activity of macrophages lavaged from patients with sarcoidosis (n=14) or idiopathic pulmonary fibrosis (n=13) and compared the enzyme activities with that of a group of normal volunteers (n=16). Cells from sarcoid patients had a mean (± 1 SD) tissue factor activity of 1,491 ± 2,160 units/5 ×10⁵ cells, as compared with a mean of 480 units (range, 140 to 1,000 units) for normal control subjects. The same cells had a mean plasma Factor VII equivalent of 4.7 ng/10⁶ cells, as compared with 0.81 ng/10⁶ cells (range, 0.2 to 2.0 ng) for the normal control subjects. The enhanced activity correlated with disease activity as judged by radiographic stage: only patients with Stage II or Stage III disease had consistently elevated procoagulant activity. There was no correlation of procoagulant activity with the percentage of lymphocytes in the alveolar fluid. Cells from patients with idiopathic pulmonary fibrosis also had increased tissue factor (mean, 2,980 ± 2,619 units) but less consistently elevated Factor VII. There was considerable variation in both procoagulant activity and cell differentials between lavage sites in 10 patients in whom 2 separate lobes were studied concurrently. In addition, we examined the plasminogen activator (PA) activities of lavaged cells and concentrated alveolar fluids. Human alveolar fluid from all normal volunteers contained PA (mean, 13.9 ± 3.4 units/ml recovered lavaged fluid) and degraded fibrin spontaneously at physiologic pH. In contrast, alveolar fluid from patients with sarcoidosis and idiopathic pulmonary fibrosis had low or absent PA activity (3.7 ±1.8 and 2.5 ± 2.2 units/ml fluid for the 2 groups, respectively). There was less spontaneous fibrinolytic activity as well. Total cell-associated PA was not clearly different between patients and normal subjects. These data indicate that concurrent changes in procoagulant and fibrinolytic pathways occur within the alveolar space of patients with interstitial lung disease. The changes suggest that some patients may be suceptible to accumulation of fibrin in the alveolar space. Re-epithelialization and scarification of this material may exacerbate the overall fibrotic process.