Organisms representative of soil, skin and fecal flora and of supragingival and subgingival flora were tested for inhibition of growth and killing by various salts (NaHCO3, NaCl, MgSO4). The antimicrobial activities of KHCO3, NaF, sodium lauryl sulfate (SLS) and chloramine T were also compared with that of NaHCO3, and the rate at which NaHCO3 exerts its bactericidal effect was studied. Suspected periodontal pathogens were more susceptible to salts than were control non-oral bacteria. Supragingival plaque organisms showed intermediate susceptibility. Periodontal pathogens were more susceptible to NaHCO3 than to NaCl; NaHCO3 and KHCO3 showed similar activity against all strains tested. Accordingly, the antibacterial activity of NaHCO3 is not simply an osmotic effect and is due to the bicarbonate ion. NaF, SLS and chloramine T had greater antimicrobial activity than NaHCO3. Supragingival bacteria required at least 6-hour exposure to 1.0 M NaHCO3 to produce 99% lethality (decrease colony-forming units by 2 log10), whereas selected periodontal pathogens were killed more rapidly (30-120 minutes). The higher the concentration of bicarbonate, the faster the lethality. Morphologic examination by transmission electron microscopy of organisms exposed to bactericidal salt concentrations revealed marked fibrillar condensations within the cytoplasm and shrinkage of the cytoplasm from the outer membrane. For NaHCO3 to be clinically effective, a high concentration must be introduced into the periodontal pocket and maintained there long enough to kill periodontal pathogens. Furthermore, NaHCO3 must be reapplied often enough to prevent recolonization by these pathogens. An advantage of NaHCO3 over NaF, SLS and other antimicrobial agents is its safety, availability and low cost.