The effects of enlargement and root planing in the treatment of systemic antibody responses were studied in patients with periodontal disease and normal subjects. Immunoglobulin G antibodies in the serum to a battery of oral microorganisms were evaluated in an enzyme immunoassay before and after treatment in 31 individuals. The majority (96%) of sick patients exhibit elevated antibodies to one or more microorganisms before enlargement scheme. Significant increases in levels of antibodies in the serum was observed in 16 of 19 patients after enlargement, while only 2 of 12 nonscalar subjects showed similar changes during follow-up intervals of up to 3 years. The bacterial specificities of the increases were found to differ between patients, however, a significant correlation for pre-existing high levels of antibodies was observed. The maximum levels of responses were observed in approximately 2 to 4 months posttreatment; antibodies returned to pretreatment levels of 8 to 12 months. The predominant organisms for the changes were observed including the black-pigmented Bacteroides spp. Eikenella corrodens, Campylobacter concisus, and Actinobacillus actinomycetemcomitans. In 18 of 19 cases, the microorganism counterpart was detected in subgingival plaque elevated antibodies when presented after treatment. These results indicated that specific changes in the responses systemic host accompany the expansion and smoothing treatment of patients with periodontal disease. These alterations in the response host can provide an additional means of success that therapy can be achieved.