We studied the genetic control of Porphyromonas gingivalis fimbriae response. Inbred mice with different H-2 haplotypes and/or different genetic backgrounds were inoculated with viable P. gingivalis 381 cells and tested for fimbria-specific T cell responses in vivo (delayed-type hypersensitivity). H-2d mice showed a strong footpad response, whereas H-2b mice showed a weak response to fimbriae from P. gingivalis. Similar evidence of genetic control was obtained with an enzyme-linked immunosorbent assay for the detection of IgG antibody in inbred mice (BALB/c, C3H/HeN and C57BL/6). Several immunoglobulin G (IgG) subclass responses were associated with H-2 in these B10 congenic mice. However, quantification of IgG antibody to fimbriae was not controlled by H-2 in B10 congenic mice. The results indicate that, in mice, the responsiveness to fimbriae of P. gingivalis can be controlled by several genes, including the H-2 complex. C3H/HeN mice were inoculated with the fimbriae intravenously, and the expression of surface antigens on spleen T cells was measured in a fluorescent antibody cell sorter. Stimulation by fimbriae resulted in a changed expression of surface antigens on T cells. Thus, the fimbriae can induce T cell activation.