The relationship of the serum antibody titer and avidity to the putative periodontal pathogens Actinobacillus actinomycetemcomitans (Aa) strains Y4 and 29523 and Porphyromonas gingivalis (Pg) strain 381 were examined in relation to clinical parameters in 26 gingivitis and 28 periodontitis patients. The relationship of antibody titer and avidity to infection with the homologous organism was also examined in a subset of 30 patients. Antibody titer was determined by an enzyme-linked immunosorbent assay, and antibody avidity was assessed using a dissociation assay. Considering all patients, there was a significant negative correlation between mean probing depth and antibody titer (r=-0.28) and avidity (r=-0.28) to Aa Y4. There was a significant positive correlation of probing depth and antibody titer (r=0.46) and avidity (r=0.46) to Pg. The correlation of antibody titer and avidity to Aa and infection with Aa Y4 (r=-0.32, r=-0.21) and Aa 29523 (r=-0.35, r=-0.39) was negative, while the correlations of titer and avidity to Pg and presence of the organisms was strongly positive (r=0.40, r=0.35). These data indicate that the relationship of serum antibody titer and avidity to clinical parameters of periodontal disease severity and the level of infection with the homologous organism appears to be different for Aa and Pg. The development of an antibody response to Aa appears to protect the individual from infection with the organism. In contrast, the development of an antibody response to Pg was not able to eliminate the infection. These results should be considered when developing a diagnostic strategy for periodontal disease utilizing the humoral immune response.