Interstitial pneumonitis includes more than a hundred diseases in which alveolitis is the main manifestation of the affected lung. Symptoms such as dry cough and exertional dyspnea, fine crackles on chest auscultation, interstitial infiltrates on chest X-ray films and CT scans, respiratory function tests, and Ga-67 scintigraphy have been used for the diagnosis and the evaluation of disease activity. However, the poor prognosis of some types of interstitial pneumonitis has not been improved. We discovered a high molecular weight mucin-like antigen, designated KL-6, which is also known as MUC1. The serum level of KL-6/MUC1 was elevated in 70-100% of patients with interstitial pneumonitis, such as pulmonary fibrosis (either idiopathic or related to collagen-vascular disorders), hypersensitivity pneumonitis, sarcoidosis, and radiation pneumonitis. The levels were significantly higher in patients with active disease than in those with inactive disease. In contrast, patients with noninterstitial lung disease did not show a significant elevation of KL-6/MUC1. Furthermore, the serum KL-6/MUC1 level was found to be an early predictive marker of the therapeutic effect of high-dose corticosteroids in patients with rapidly progressing idiopathic pulmonary fibrosis. These results indicate that KL-6/MUC1 may be a useful serum marker for the diagnosis and monitoring of patients with interstitial pneumonitis.