Adherence is an early step in infection by microbial pathogens. The binding of the common oral bacteria Streptococcus mutans, the main etiological agent of dental caries, has recently been investigated 1 Kelly C.G. et al. A synthetic peptide adhesion epitope as a novel antimicrobial agent. Nat. Biotechnol. 1999; 17: 42-44 Crossref Scopus (97) Google Scholar . A synthetic peptide corresponding to residues 1025–1044 (p1025) from the S. mutans nonfimbrial cell surface adhesin was previously shown to inhibit binding between S. mutans and salivary receptors in vitro. The aim of this study was to determine whether topical application of p1025 as an anti-adhesive agent could be therapeutic and could prevent S. mutans colonization in vivo. Volunteers were pretreated with an antibiotic to deplete oral flora and eliminate S. mutans. A control peptide, saline or p1025 was applied to the teeth and given as a mouthwash. Samples of dental plaque and saliva were collected, and the amount of S. mutans was determined. In contrast to the control treatments, recolonization of the oral cavity by S. mutans was prevented by p1025; this was specific, as recolonization by another Gram-positive oral bacteria did occur. The relatively long-term resistance (>120 days in three of four volunteers) was not explained by persistence of the peptide or the development of the immune response. The authors suggest that initially the inhibition might result from interference of the adhesin–receptor interaction but that the inhibition of colonization might be due to microbial competition by other plaque bacteria occupying the S. mutans niche.