Experimental autoimmune sialoadenitis was induced in PL/J (H-2u) mice by intradermal immunization with human carbonic anhydrase II (CAII) and adjuvant containing monophosphoryl lipid A and trehalose diorynomycolate. Mice immunized with CAII showed a significant increase in the number and size of foci with lymphocytic infiltration in the salivary gland compared with mice immunized with adjuvant alone and untreated mice. In mice immunized with CAII, lymphocytic foci were observed around intercalated and intralobular ducts in the salivary glands, resulting in atrophy and replacement of acinar units. The epithelial cells of salivary ducts adjacent to the lymphocytic foci showed both degenerative and regenerative changes. Similar lymphocytic infiltrations were observed in the pancreas and kidney of a few mice immunized with CAII. Among several mouse strains with different H-2 haplotypes (p, q, r, s, and u), strains bearing H-2s and H-2u were susceptible to CAII-induced sialoadenitis. These results indicate that sialoadenitis induced by the immunization of CAII in mice may serve as a disease model of Sjögren's syndrome and that CAII or its derived peptides in association with the MHC may be one Ag recognized by an autoimmune response in this syndrome.