The comparative in vitro activities of 11 iodonium salt compounds, 0.12% chlorhexidine, and four antimicrobial agents against 322 anaerobic and fastidious potential dental and periodontal bacterial pathogens were studied. Iodonium salts 3, 4, 5, 9, and 10 had in vitro activities comparable to that of chlorhexidine against most isolates. These compounds may be suitable for incorporation into an oral mouthwash.Biodiversity studies of subgingival plaque estimate that more than 400 different species may colonize the subgingival region (7,8,12), with approximately 20% of these species not being cultivable by current methods. These microbes occupy microbiologically different ecological niches in the oral cavity. Subsets of these isolates, still not fully defined, are potentially pathogenic and cause a variety of orally related diseases. Periodontal diseases, including gingivitis and periodontitis, are chronic conditions that develop as a result of bacterial accumulations (plaque) on the teeth and gingivae. Their prevalence increases with increasing age, and approximately 50% of adults in the United States have gingivitis around three to four teeth at any given time. Moreover, 30% develop periodontitis and approximately 3% have advanced or aggressive periodontitis (1).Gingivitis is of polymicrobial origin and can be reversed with good oral hygiene. Periodontitis is a major cause of tooth loss in humans. These diseases are associated with an alteration of the healthy oral flora and an increase in the isolation of periodontal pathogenic species, especially anaerobic bacteria such as Bacteroides forsythus (Tannerella forsythensis), Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and a variety of uncultivable spirochetes (1,8,13). Therapies include adherence to good oral hygiene, dental procedures, and the administration of topical and oral antimicrobial agents.Another adjunctive, popular approach is consumer selfadministration of mouthwashes which contain a variety of ingredients to kill oral bacteria, including alcohol, cetylpyridinium chloride, zinc chloride, benzoic acid, benzalkonium chloride, eucalyptus oil, and thymol. Chlorhexidine gluconatecontaining mouthwashes (e.g., Perio Rx) are available with medical or dental prescriptions. These have the ability to bind and penetrate plaque biofilm and prevent bacterial aggregation, slow multiplication, and extract endotoxins.Iodonium salts are organic cations with profound and wideranging physiological actions that are based on the inhibition of pyrroloquinoline quinone (or methoxatin 1), a bis(quinone) tricarboxylic acid that is an organic cofactor in the biological redox cycling process (2). These activities include mitochondrial toxicity causing blockage of gluconeogenesis, inhibition of the respiratory burst in stimulated neutrophils, and the inhibition of nitric oxide synthase (2) and broad-spectrum inhibitory activity against bacteria, fungi, yeasts, and small viruses (patent disclosure). Preliminary data (supplied by Ch...