BACTERIAL-NEUTROPHIL INTERACTIONS may be critical determinants of virulence in periodontal diseases. This study was undertaken to examine the ability of major bacterial species from the human oral cavity to inhibit (1) peripheral blood neutrophil chemotaxis, (2) chemotactic formylmethionyl peptide binding, and (3) phagocytosis. Included were cultured supernatants and sonic extracts obtained from strains of Capnocytophaga, Bacteroides gingivalis, Fusobacterium nucleatum, Bacteroides asaccharolyticus, Capnocytophaga species, Actinobacillus actinomycetemcomitans, Neisseria, Actinomyces viscosus, Bacterionema matruchotii, Streptococcus mitis, Streptococcus mutans, and Streptococcus sanguis. Chemotaxis was measured using Boyden chambers; phagocytosis was determined using Staphylococcus aureus as the indicator organism and radioactive chemotactic peptide binding was assessed by a rapid filtration assay. None of the test organisms were cytotoxic to neutrophils or inhibited neutrophil phagocytosis. Capnocytophaga species., Bacteroides species., A. actinomycetemcomitans, and F. nucleatum produced factors which specifically inhibited neutrophil chemotaxis. Activity was lost after dialysis. Extracts of Bacteroides species, A. actinomycetemcomitans and F. nucleatum, which were not chemotactic by themselves, inhibited binding of chemotactic peptide suggesting that in vitro chemotaxis inhibition was mediated by nonchemotactic components that compete for the chemotactic factor receptor on the neutrophil. The exception was Capnocytophaga which appeared to inhibit chemotaxis by inhibition of a post-binding event. Such chemotactic inhibitors from periodontopathic organisms that inhibit neutrophil function may be important determinants of virulence.