Changes in the content and molecular state of secretory leukocyte protease inhibitor (SLPI) in the airways in chronic airway diseases were studied. SLPI in bronchoalveolar and bronchial lavage fluids (BALF and BLF) from normal subjects and patients with diffuse panbronchiolitis (DPB), and in mucoid sputa from patients with emphysema and in purulent sputa from DPB patients were examined by ELISA and Western blotting. Results showed that in the BALF and BLF of normal subjects, the SLPI/alpha 1-protease inhibitor (alpha 1-PI) ratios (M/M) are about 0.6 and 6, respectively and the neutrophil elastase inhibitory capacity of BLF is mainly due to SLPI. In the BALF and BLF of DPB patients, both the elastase activity and alpha 1-PI level are increased, but the SLPI level is decreased. In purulent sputa, the elastase activity was found to be 430-fold that in mucoid sputa and the alpha 1-PI level to be 3.5-fold that in mucoid sputa, but the SLPI level was slightly lower in the mucoid sputa. Analysis by Western blotting showed that in BLF from normal subjects and mucoid sputa, SLPI is present in an intact form and in complexes with other substances, whereas in BLF and purulent sputa from DPB patients, SLPI is present in a degraded form and in complexes with other substances, but not in the intact form. These results indicate that SLPI is the main protease inhibitor in the airways of both normal subjects and patients with hypersecretory respiratory diseases without infection, but that its level is insufficient to overcome the increased protease burden in the airways of DPB patients.