Bacteroides gingivalis is associated with various forms of periodontal disease. To assess the role of the immune response in modulating B. gingivalis-associated periodontal disease, the effect of immunization of B. gingivalis-induced periodontal bone loss was evaluated in gnotobiotic rats. Male Sprague-Dawley rats immunized with various doses of whole cells or sham-immunized with incomplete Freund's adjuvant were monoinfected with B. gingivalis in carboxymethylcellulose by gavage. Two additional groups served as either sham-immunized or untreated germ-free controls. Forty-two days after infection, all rats were killed, periodontal bone level was assessed morphometrically and radiographically, and gingival proteinase (mammalian collagenase and acid cathepsin) activity was assessed biochemically. B. gingivalis was present in oral samples from all monoinfected rats, and no contaminating bacteria were detected in any oral or fecal sample. Animals immunized with B. gingivalis cells had elevated serum and saliva antibodies to whole cells and partially purified fimbriae from B. gingivalis. Infected sham-immunized rats had significantly more periodontal bone loss than noninfected controls, whereas the periodontal bone level in infected rats immunized with 10(10) B. gingivalis cells was similar to that of the noninfected controls. The activities of gingival collagenase and cathepsin B and L were high in sham-immunized infected rats and low in all other animal groups. In conclusion, it is possible to reduce B. gingivalis-induced periodontal tissue loss in gnotobiotic rats by immunization.