In order to study the role of T lymphocytes and B lymphocytes in the development of marginal periodontitis, experiments were performed on specific-pathogen-free (SPF) rats with various immunologic profiles. The study comprised nude (congenitally T lymphocyte-deficient), thymus-grafted nude (T-lymphocyte reconstituted), anti-mu treated (temporarily B lymphocyte-deficient), and normal rats. When they were 5 to 9 weeks old, some of the rats were inoculated with Actinomyces viscosus. Bacteroides gingivalis and a strain of oral spirochetes; 90 days later they were killed. A. viscosus and B. gingivalis colonized readily, but the spirochete strain could not be established permanently in the oral cavity of the rats, 95% of the inoculated rats raised serum IgG or IgM antibody against one or more of the microorganisms; nude rats tended to raise less antibody than the three other experimental groups. Inoculated rats had significantly less periodontal bone support than controls. Anti-mu treated inoculated rats had significantly less periodontal bone support than nude and normal rats, whereas no difference was found between normal, nude, and thymus-grafted rats. It is concluded that permanent T-lymphocyte deficiency did not interfere with the development of periodontal disease in this model, whereas a temporary and moderate reduction in B-lymphocyte numbers seemed to predispose for aggravation of periodontal bone loss.