Dental caries is the most prevalent human infection. It is a multifactorial disease in which the microbial composition of dental plaque plays a major role in the development of clinical symptoms. The bacteria most often implicated in the development of caries are that group of streptococci referred to as the mutans streptococci, in particular Streptococcus mutans and Streptococcus sobrinus. One approach to the prevention of caries is to reduce the numbers of mutans streptococci in plaque to a level insufficient to support demineralization of the tooth. In this study, zoocin A, a peptidoglycan hydrolase, combined with lauricidin, a cell membrane active lipid, was shown over a 72 h period to selectively suppress the growth of S. mutans in a triple species biofilm. Growth of the non-target species Streptococcus oralis and Actinomyces viscosus was not inhibited. In treated systems the amount of extracellular polysaccharide matrix produced was much reduced as determined by use of fluorescein isothiocyanate conjugated wheat germ agglutinin. The pH of treated biofilms remained above neutral as opposed to a value of 4.3 in untreated controls. We conclude that use of antimicrobial compounds that specifically target cariogenic bacteria should be further explored.