The localization of I-A-like class II major histocompatibility complex (MHC) molecules and cells of the monocyte/macrophage lineage was studied immunohistologically in the trachea and lungs of conventional, specified pathogen-free (SPF) and germ-free rats. In the three groups of animals I-A-like class II MHC molecules occurred in epithelia of the bronchus-associated lymphatic tissue (BALT), in B lymphocytes, in dendritic-shaped and elongated interstitial cells and in type II pneumocytes. Conventional and SPF rats were distinguished from germ-free animals only by the larger number of class II MHC-positive respiratory epithelial cells in the lower trachea and main bronchi. The distribution of monocytes/macrophages (ED1-positive cells) did not differ between the groups. After systemic treatment of SPF rats with interferon-gamma class II MHC molecules were newly induced in all respiratory epithelia and in the endothelium of large vessels. In addition, interferon-gamma sometimes led to pulmonary infiltration and caused class II-positive activated monocytes to accumulate in medium-sized pulmonary vessels and in alveolar capillaries. It is concluded that the microbial status does not qualitatively alter the distribution of class II MHC molecules and monocytes/macrophages in rat respiratory organs. Interferon-gamma can, however, provoke profound changes.