Immunological studies examining the homogeneity of the major antigenic components of P. gingivalis have suggested 3 serotypes and have indicated a limited distribution of the serotypes in an individual patient. These studies prompted us to define the immunodominant antigens and distribution of immune responses to P. gingivalis serotypes. Serum IgG antibody levels in periodontitis patients in the present study were most frequently elevated above the normal subjects when tested against P. gingivalis serotype A (i.e., 33277). Nearly 1/3 of the patients showed significantly elevated antibody to multiple serotypes of the P. gingivalis apparently resulting from cross-reacting antigens. We determined distinctive differences among outer envelope protein and antigen patterns obtained from the three serotypes. Moreover, the results identified considerable similarities in the qualitative and quantitative antigen response patterns among patients to a particular serotype. There was a strong positive correlation between IgG antibody levels (ELISA) and the total level of reactivity determined in the immunoblots, as well as a positive correlation to the proportion of antibody to particular antigens. These findings suggest that responses to these antigens comprised a major portion of the response to the intact microorganism. Additionally, the detection of antibody to particular antigen bands was indicative of early responses to each of the P. gingivalis serotypes. The results of our study indicate that a subpopulation of periodontitis patients develop an extensive serum antibody response often to multiple serotypes of P. gingivalis and may define a patient population with a P. gingivalis disease. Finally, our results indicate a more consistent antigenic composition for P. gingivalis which may enhance the potential for strategies to immunologically interfere with disease caused by this microorganism.