For the development of vaccines against oral and pharyngeal pathogens invading the mucosal epithelia, both secretory and serum immunoglobulin A (IgA) and IgG antibodies and cytotoxic T lymphocytes (CTL) have been induced. We used a novel approach, targeted salivary gland (TSG) immunization, using plasmid pcDNA3/fimA, coding for Porphyromonas gingivalis fimbriae. Expression of subunit protein, fimbrillin, was observed in eukaryotic cells growing in vitro following transfection with pcDNA3/fimA. In this study, we obtained good humoral and cell-mediated immune responses in BALB/c mice by TSG administration using the above-mentioned DNA vaccine. The production of fimbria-specific IgA and IgG antibodies in saliva and serum IgG antibody was significantly stimulated by TSG immunization. Injection of DNA vaccine into salivary gland elicited high-level production of antigen-specific IgG antibody, similar to that induced following intramuscular immunization. The major IgG subclass that recognized fimbriae was IgG2a in serum from pcDNA3/fimA-immunized mice. Reverse transcription-PCR analysis of mononuclear cells from salivary glands showed that levels of Th2 cytokine-specific mRNA were higher in the immunized group than in the nonimmunized group. In addition, TSG DNA immunization resulted in the generation of antigen-specific CTL in spleen. These results indicate that TSG immunization with plasmid DNA may represent a genetic immunization strategy against infection by oral and pharyngeal pathogens that may invade local, mucosal surfaces.