An in vivo clinical program investigated the relationship among oral microorganisms, bacterial plaque, and calculus formation. Benzethonium chloride, cetylpyridinium chloride, and Vancomycin provided a moderate reduction in bacterial plaque accumulation (30 to 35%). Hexachlorophene was relatively ineffective. One antibiotic, CC 10232, consistently furnished substantial reductions in plaque formation (70 to 77%) and calculus formation (75%). Only Vancomycin significantly reduced the gram-positive population. None of the antimicrobial agents caused changes in the staphylococcal or yeast populations.