Streptococcus mutans is a major cariogenic inhabitant of the high cell density oral biofilm (dental plaque). In previous studies, we showed that production of one of its virulence factors, the bacteriocin mutacin IV, was regulated by high cell density as well as the competence regulatory system ComED. In this study, we utilized luciferase fusions and real-time reverse transcriptase polymerase chain reaction (RT-PCR), to demonstrate that high cell density and ComED also regulate an uncharacterized group of mutacin and mutacin-like genes. Under high cell density or in the presence of externally added competence-stimulating peptide (CSP), gene expression increased 10- to 30-fold. Interestingly, high cell density was able to bypass the requirement for CSP addition. However, both cell density and CSP-dependent gene expression had a strict requirement for the ComE response regulator.