Periodontal diseases comprise a heterogeneous group of infections that are difficult to distinguish on a clinical basis alone. The purpose of the present investigation was to group periodontitis subjects according to their elevated serum antibody levels to specific subgingival species. A total of 119 subjects (19-70 years) with evidence of prior periodontal destruction were monitored at 2-month intervals (maximum 8 visits), prior to therapy, using clinical parameters measured at 6 sites per tooth. The probing attachment level was measured twice at each visit, and an increase of >2.5 mm at a site was used to define subjects with progressing disease. Serum samples were obtained from each subject at each visit and the level of antibody determined by enzyme-linked immunosorbent assay to 12 subgingival species. Subgingival plaque samples were taken from the mesial aspect of all teeth in each subject at each visit, and the levels of 14 different subgingival species were determined using a colony-lift method and DNA probes. Subjects were grouped by cluster analysis of their elevated antibody levels using a simple matching coefficient. Ninety-two subjects fell into 9 clusters with 100% similarity; 29 subjects in one cluster group exhibited elevated antibody to none of the test species. Seven subjects in a second cluster group showed elevated antibody to Bacteroides forsythus. Subjects in the other 7 clusters showed elevated antibody to Actinobacillus actinomycetemcomitans serotype a only or in combination with B. forsythus, A. actinomycetemcomitans serotype b, Prevotella intermedia or Porphyromonas gingivalis. Subjects in different cluster groups differed with respect to age, number of active sites, levels of gingivitis, prior periodontal destruction and levels of 11 of 14 microbial species tested. Subjects with multiple elevated antibody levels had significantly more active sites than subjects with 0 or 1 elevated response. The 23 early-onset periodontal disease subjects were confined primarily to 2 clusters or were unclustered and 78% had multiple elevated antibody levels. There appeared to be a finite number of frequently detected antibody patterns that may be useful in categorizing periodontitis.