While studying the oral bacterial biota of mice, we observed an unidentified streptococcus (TG) that eventually became the dominant species of the oral cavities of all other mice in our animal facility. We found that the strain is indigenous to Jackson Laboratory mice but is absent in animals from Charles River Laboratories. TG was also transmitted from artificially contaminated BALB/c mice to the oral cavities of 4 other mouse strains. Streptococcus sp. TG stimulated the secretory and systemic immune systems of artificially contaminated Charles River BALB/c mice but did not provoke clinical symptoms. The increase in antibody level to TG did not prevent its colonization and persistence in these mice. In mice from Jackson Laboratory, the secretory and systemic immune response to TG was significantly lower. In vitro, Streptococcus sp. TG inhibited murine oral lactobacilli and staphylococci, probably due to the production of hydrogen peroxide.