Serum levels of a high molecular weight circulating antigen KL-6, detected by means of a sandwich assay using a monoclonal antibody KL-6 against a sialylated carbohydrate antigen, were evaluated for usefulness in monitoring the activity of interstitial pneumonitis. Abnormally high levels of KL-6 antigen were observed in the sera of 34 (58 percent) of 59 patients with interstitial pneumonitis. There was no significant correlation between serum values of KL-6 antigen and LDH activity. There was a positive correlation between KL-6 antigen levels and the degree of clinical disease activity as measured by 67Ga-citrate scintigram and the clinical course. Though this is a preliminary study, these observations suggest that the serum level of KL-6 antigen may be a useful indicator of disease activity in patients with interstitial pneumonitis. It does not appear to be useful, however, in the differential diagnosis of interstitial pneumonitis from malignant and nonmalignant diseases.