The interaction of the human salivary glycoprotein EP-GP with a number of oral bacterial species, following incubation with human whole saliva, has been investigated. EP-GP could be detected with a specific monoclonal antibody, by means of ELISA or by electrophoresis in combination with Western Transfer. The results indicated that EP-GP is bound only by Streptococcus salivarius, and not by the other tested strains of bacteria, Actinomyces viscosus, A. naeslundii, Actinobacillus actinomycetemcomitans, Bacteroides fragilis, S. gordonii, S. oralis, S. sanguis, S. mitis, S. mutans, S. sobrinus, S. rattus, S. constellatus, and S. anginosus. Binding of EP-GP to S. salivarius is mediated by a protein-protein interaction, which was found to be pH-dependent with a maximum binding between pH 5 and 6. For further characterization of the binding of EP-GP to S. salivarius, four mutants were tested, each of them lacking different cell wall antigens. EP-GP was bound to all mutants in amounts comparable with the wildtype, in spite of the different surface antigen compositions. We were able to identify a 27-kD EP-GP binding protein, by extraction of S. salivarius-cell wall antigens and electrophoretic techniques. In addition to EP-GP, S. salivarius also bound two other salivary proteins, namely, secretory IgA and low-molecular-weight mucin (MG-2).