Immunochemical studies of post-mortem lung tissue from a patient suffering from diffuse pulmonary interstitial fibrosis were conducted. Identifiable deposition of IgG on the alveolar septa was noted by immunoperoxidase and immunofluorescein methods. The antemortem serum obtained from the patient showed high affinity immunologic binding to normal human lung tissue. An antibody-antigen reaction was also detectable by microcomplement fixation procedure with buffer extracts of normal lung tissue, while normal pooled serum showed no significant reaction. These findings, in addition to the gross, light microscopic, and electron microscopic observations, strongly suggest that a humoral antibody mediated reaction is one of the underlying pathogenetic mechanisms eliciting the morphologically and clinically observable manifestations of diffuse interstitial pulmonary fibrosis.