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The effect of age on the humoral response to Porphyromonas gingivalis was assessed in groups of adults (25 to 54 years and 55 to 74 years) with periodontal disease and compared with that in age-matched healthy controls. To determine whether there was an antibody response against P. gingivalis, we measured serum antibodies against whole cells of P. gingivalis 381, A7A1-28, and W50. In addition, antibody levels against purified P. gingivalis outer membrane proteins (i.e., the 43-kDa fimbrial protein and a 75-kDa protein) were also evaluated. Elderly subjects showed the same response to P. gingivalis as younger subjects. Immunoglobulin G (IgG) antibodies to both purified proteins were also elevated in both diseased groups as compared with the normal groups. Total serum IgG, IgA, and IgM levels were also determined by an enzyme-linked immunosorbent assay for all four groups. Total serum IgG levels were elevated in older adults with periodontitis and total IgA levels were elevated in both groups of older adults compared with the younger groups of similar disease status. Total serum IgM levels were comparable for the four groups. Antinuclear antibody titers were assessed in the two groups of older adults and were also found to be higher for the group with periodontitis. These studies show that older adults as well as younger adults have markedly elevated specific antibodies of the IgG and IgA classes to antigens of P. gingivalis, a putative pathogen in both groups. Furthermore, older adults with periodontitis have significantly elevated levels of total serum IgG which may possibly be related to higher levels of autoantibodies.