Plaque samples were obtained from 13 children receiving long-term therapy with benzathine penicillin for the prevention of rheumatic fever recurrences, 31 children receiving oral sulfadiazine for the same purpose, and 29 untreated siblings. The therapies were found to have no effect upon the proportions of Streptococcus mutans or lactobacilli in dental plaque, upon the percentage of children harboring the organisms, nor upon the susceptibility of the organisms to penicillin and sulfadiazine. Of the S. mutans strains tested, 97% had a minimnal inhibitory concentration of penicillin G of less than 48 ng/ml and, of the lactobacillus strains tested, 96.8% had a minimal inhibitory concentration of less than 1,600 ng/ml. All strains of both organisms were profoundly resistant to sulfadiazine.Children receiving 200,000 U of oral penicillin daily for rheumatic fever prophylaxis have been reported to experience reductions in the incidence of dental caries of up to 56% as compared with their untreated siblings (13, 18). Handelman and Hawes have reported that the oral penicillin therapy had no effect on the number of salivary lactobacilli (12) and that the penicillin resistances of the total flora, the streptococci, and the staphylococci in the salivas of the antibiotic users were higher than those in the untreated siblings (11). They did not study the effect of oral penicillin on Streptococcus mutans; consequently, it is not known whether the caries-inhibiting effect of that agent (13) resulted from its action on that organism. Furthermore, they did not examine the dental plaque flora, which is more intimately associated with the development of the carious lesion than is the salivary flora.