The purpose of this study was to assess whether mononuclear cell abnormalities exist in salivary glands from autoimmune Bio-Breeding (BB) rats. Frozen sections of gland tissues were prepared from five diabetes-resistant BB rats (BB-DR), from five BB rats with diabetes (BB-DP) and from five Wistar rats. A panel of six monoclonal antibodies was used to identify membrane antigens associated primarily with monocytes (ED1), mature tissue macrophages (ED2), lymphoid macrophages (ED3), MHC class II (Ia) antigen (OX6), CD5+ T lymphocytes (OX19), and rat B lymphocytes (OX33). Normal submandibular, sublingual and parotid glands contained few ED1-positive cells, usually two or fewer per field. Tissue macrophages identified by clone ED2 comprised a major mononuclear cell subset in both Wistar and BB rats. However, the number of ED2-positive mononuclear cells was significantly depressed in the submandibular and parotid glands from BB-DR and BB-DP animals, being present in quantities 25-50% of those observed in glands from normal Wistar rats (p < 0.001). In contrast, 25- to 30-fold greater numbers of ED3-positive macrophages were observed in submandibular glands from BB rats (p < 0.001). MHC class II (Ia) antigen expression also was 4- to 6-fold greater in BB rat submandibular glands, compared to Wistar rats (p < 0.001). CD5+ T-lymphocytes were rare or entirely absent in BB sublingual glands (0 to 1 cell per 0.87 mm2 field), compared to 47 cells per field from Wistar sublingual glands. No B lymphocytes were identified with antibody OX33 in any of the rat strains. These findings indicate that BB rat salivary glands differ significantly from Wistar salivary glands. In BB rats there is a rich population of ED3-positive macrophages and T lymphocytes in submandibular gland, low quantities of T lymphocytes in sublingual gland, and fewer ED2-positive macrophages in all three major salivary glands. These differences in mononuclear cell subpopulations may also influence salivary gland function in mucosal immunity.