In the present study we sought to determine whether serum antibody was present against microorganisms which predominate in the subgingival flora of young adults with generalized severe periodontitis (SP). Subjects with SP were often seropositive for Eubacterium brachy, Fusobacterium nucleatum E3C22, and Peptostreptococcus micros, whereas subjects with juvenile periodontitis (JP) and subjects with healthy periodontium (HP) were not. Both SP and JP subjects were more frequently seropositive for Bacteroides gingivalis, F. nucleatum D52B16, and F. nucleatum E1D1 than were HP subjects. The data were most striking for B. gingivalis, for which both the incidence and the magnitude of specific antibody was clearly elevated for SP and JP subject groups. However, SP subjects generally had either a high antibody titer or no detectable titer. In contrast, JP and HP subjects generally had at least very small amounts of antibody. Except at very low levels of antibody, neither SP nor JP groups differed significantly from the HP group for antibody to Eubacterium nodatum, Bacteroides intermedius (homology group 4197 or 8944), or Lactobacillus minutus antibody. There was a high frequency of antibody to E. nodatum, with very high titers in all groups despite the fact that this organism is rarely found in HP subjects. For Eubacterium timidum, the JP group was clearly more frequently seropositive than the HP group. Despite high levels of L. minutus in subgingival flora, none of the 50 SP subjects had a detectable antibody titer, and only 4 of the HP and JP subjects had detectable antibody. These results indicate that many organisms in the subgingival flora elicit antibody responses. B. gingivalis is probably the best example among the species tested. However, some organisms that are present in high concentration, e.g., L. minutus, apparently fail to induce significant antibody responses.