The relationship between local and systemic host antibody responses, colonization of subgingival plaque by periodontal disease-associated microorganisms and the progression of periodontal disease was assessed in 61 patients. Serum antibody levels to a battery of oral microorganisms were determined by an enzyme-linked immunosorbent assay (ELISA), and an organism to which each patient exhibited a significantly elevated IgG response was chosen for further study. To detect the presence of the specific microorganism, plaque samples were obtained and examined using a seroELISA. Static crevicular fluid (SCF) samples were also obtained from all teeth and analyzed for IgG antibody to the homologous organism. A modification of the standard ELISA using biotin and avidin allowed a 5- to 10-fold increase in sensitivity for detection of IgG antibody in serum and SCF. Comparison of the distribution of elevated SCF antibody and the presence of the corresponding microorganism in each patient showed that the proportion of agreement was 54 to 78% in the samples. Schematic representation of the temporal relationship between the organism, the host response and disease activity were prepared to explain the results obtained in investigations of these parameters and to provide a testable hypothetical framework for future studies.