L(plus)-Lactate dehydrogenase-deficient mutants of Streptococcus mutans are being tested for their potential to serve as effector strains in the replacement theory of dental caries. Various studies have been performed, or are planned, to characterize both the pathogenic potential of the mutants and their ability to compete with naturally occurring strains of Strep. mutans in the oral cavities of susceptible hosts. In particular, it has been shown that the mutants produce less acid than their parent, BHT-2, from metabolism of glucose, sucrose, and a variety of other carbon sources, and hence should be less cariogenic. The mutants colonize the oral cavities of germfree and conventional Sprague-Dawley rats to the same extent as their parent, but produce a significantly lower incidence and severity of dental caries. Moreover, rats which have been colonized by a mutant strain appear resistant to superinfection by the parent strain. The ability of the mutants to exclude Strep. mutans of other serogroups is currently being studied. Similar studies of the pathogenic and competitive nature of the mutants are also being planned using monkeys as the host. Finally, the biochemical basis of the mutants' low acid-producing phenotype has been partially characterized, and it is hoped that a fermentation balance can be established for the metabolism of glucose.