Immunologic defense factors in the human olfactory mucosa were localized immunohistochemically. Olfactory epithelium was identified with an antiserum to olfactory marker protein, specific for olfactory receptor neurons. Constituents of the secretory immune system, including IgA, IgM, secretory component, and J chain, were localized in the acinar and duct cells of Bowman's glands and in the mucociliary complex. In addition, B lymphocytes in the lamina propria near Bowman's glands displayed immunoreactivity for IgA, IgM, and J chain. Immunostaining also localized other humoral factors. Immunoreactivity for IgG was present throughout the stroma and in B lymphocytes in the lamina propria. Antibody to IgD stained numerous B lymphocytes clustered below the basement membrane. Antibody to IgE stained similarly distributed cells; toluidine blue staining demonstrated that many were mast cells. In addition, antibodies to IgD and IgE stained occasional intraepithelial B lymphocytes or mast cells. Two antimicrobial proteins, lactoferrin and lysozyme, were localized in Bowman's glands and the mucociliary complex. Thus, the human olfactory mucosa, which provides a direct neural route for pathogens to the brain, is a site for synthesis and secretion of immune and other defense factors.