Recombinant murine interferon-gamma (IFN-gamma) was administered in 6 to 9 daily intraperitoneal injections to B10.BR (H-2k) mice. The distribution of some selected class I and II major histocompatibility complex-determined antigens was localized by immunocytochemistry with the use of anti-H-2Kk and anti-IAk monoclonal antibodies and avidin-biotin-peroxidase in unfixed, frozen lungs for light microscopy and in fixed lungs for electron microscopy. In normal control mice no class I antigens were detected in the lung either by light microscopy or by ultrastructural immunocytochemistry. After 6 to 9 days of IFN-gamma administration, class I antigens were detectable on the endothelium of major vessels and diffusely throughout the alveolar region, presumably on alveolar capillary endothelium. Class I antigens did not withstand chemical fixation, therefore, could not be localized at the ultrastructural level. In normal, control mice class II antigens were detectable on a few interstitial macrophages, on some circulating monocytes, and on elongated cells adjacent to airways and major vessels. After 6 to 9 daily injections of IFN-gamma, larger numbers of macrophages and elongated cells, believed to be dendritic cells, were present around major airways and vessels. In addition, numerous round cells stained throughout the alveolar region. By electron microscopy these round cells included intraalveolar macrophages, although not all alveolar macrophages expressed IAk, circulating monocytes in capillary lumens, and type II pneumocytes. Type I pneumocytes had no detectable IAk. Reaction product in type II cells was limited to the basolateral membranes. Airway epithelium and endothelium remained unstained. These observations indicate that in addition to monocytes/macrophages IFN-gamma induces the expression of class II antigens on type II pneumocytes.