Local oral passive immunization in human subjects with a monoclonal antibody (MoAb) raised against the 185-kD antigen I/II from S. mutans significantly reduced or prevented oral colonization of an exogenous strain of the organism. In subjects sham-immunized with either saline or an unrelated MoAb, however, significantly greater proportions of S. mutans persisted for a longer duration than in those immunized with the specific anti-streptococcal MoAb. Recolonization of indigenous S. mutans after this organism was reduced to undetectable levels by an antimicrobial agent has also been completely prevented with specific MoAb. Indeed, S. mutans was not detected for a period of over 1 year, as compared with recolonization within 10-82 days in the control subjects. The specificity of MoAb in preventing colonization of the streptococci was studied with four MoAb. This revealed that: (1) the sub-class of antibody is not an essential factor, as both MoAb Guy's 1 and 13 prevented colonization, although Guy's 1 is an IgG2a and Guy's 13 is an IgG1 class of antibody; (2) serotype specificity is important, as MoAb Guy's 9, which only recognizes S. sobrinus (serotypes d and g), does not prevent colonisation by S. mutans (serotype c); (3) neither protein nor carbohydrate nature of the putative adhesin was a determining factor, because MoAb Guy's 1 recognizes a carbohydrate and Guy's 13 a protein determinant and both MoAb prevented adherence of S. mutans; and (4) epitope specificity appears to be the most important factor in preventing adherence of S. mutans, as MoAb Guy's 11 and 13 share the same serotype specificity and both recognize a protein determinant, yet only Guy's 13 prevents colonisation. The long duration of protection from re-colonization by indigenous S. mutans, lasting about 1 year after application of the specific MoAb was stopped, cannot be accounted for by functional MoAb remaining on the teeth. We suggest that initially the MoAb prevents colonization by S. mutans and that the ecological niche vacated by this streptococcus is filled by other organisms from the oral flora, thereby discouraging re-colonization by S. mutans.