Pulmonary surfactant is synthesized and secreted by alveolar type II cells. The major components of surfactant are phospholipids and four distinct surfactant-specific proteins: SP-A, SP-B, SP-C, and SP-D. The concentrations of SP-D and SP-A were measured in sera of patients with idiopathic interstitial pneumonia (IIP), by enzyme-linked immunosorbent assay with monoclonal antibodies against human SP-D and SP-A. The concentrations of SP-D and SP-A in samples from the patients were, respectively, 5.7 and 2.8 times higher than those in samples from healthy volunteers; 86.2% and 71.4% of the patients had concentrations of SP-D and SP-A, respectively, that were more than 2 standard deviations greater than the mean of the control values. Moreover, the serum SP-D and SP-A concentrations appeared to reflect the disease activity of IIP. There was a negative significant correlation between the concentrations of SP-A in serum and in bronchoalveolar lavage fluid. These results suggest that SP-D and SP-A, which are primarily secreted from alveolar type II cells into the alveolar lumen, can enter the bloodstream easily due to injury at the alveolar-capillary membrane. We conclude that measurement of SP-D and SP-A in sera can provide an easily identifiable and useful clinical marker for the diagnosis of IIP, and can be used to predict the disease activity of IIP.