An antimicrobial system that inhibited the growth of lactobacilli and certain other organisms in human saliva was described over 30 years ago (1,2). This system could be distinguished from lysozyme (3-7) and IgA (8). Antilactobacillus activity was present in sterile, cell-free parotid or submaxillary saliva (6, 9), suggesting that the source of the antimicrobial system was the salivary glands and that the phagocytes and microorganisms of saliva were not essential under the conditions employed. Attempts to define the nature of this antimicrobial system were unsuccessful until it was found to contain at least two components: a heat-stable, dialyzable component and a heat-labile, nondialyzable component (7, 10, 11). The heat-stable, dialyzable component could be replaced by thiocyanate ions in the concentrations present in saliva (11,12). Iodide ions also were effective; however, the concentration required was outside the physiological range (11, 12). The heat-labile, nondialyzable component was found to be the salivary peroxidase; it could ke replaced t~y bovine milk lactoperoxidase (LPO) L (13) (an enzyme immunologically and chemically indistinguishable from bovine salivary gland peroxidase [14]) or by the peroxidase of human parotid saliva (8) in amounts equivalent to those present in saliva.The addition of reagent H202 was not required when lactobacilli were the test organisms; a requirement for H202 was suggested, however, hy the inhibitory effect of catalase (13). Lactobacilli and the other organisms designated by Orla-Jensen as lactic acid bacteria (e.g. streptococci, pneumococci) form and secrete H~O2 into the medium (15). These organisms, in general, do not contain heine and thus utilize flavoproteins for terminal oxidations with the reduction of oxygen to H~O2. The spectrum of organisms whose growth is inhibited by the peroxidase-mediated antimicrobial system of saliva is extended to non-H~_Oe-generating organisms (e.g. Escherichia c61i, Staphylocoecus aureus) when H20,_, or an H20,_,-generating system is added to the reaction mixture (16).The studies outlined above suggest that saliva may contain an antimicrobial system that consists of three components, the salivary peroxidase (LPO), thiocyanate ions, and He()..,, and that microbial metabolism can serve as a source of HoO~ for this system. The importance of viridans streptococci in the control of the oral microbial * q his project was supported in part by grants AI 07763, HD 02266, and AM 1000 from the U. S. Public Health Service.1Abbre-,iations used in this paper: KRP, Ca*+-free Krebs Ringer phosphate; LPO, lactoperoxidase; POPOP, 1,4-bis-I2-(5-phenyloxazolyl)]henzene; PPO, 2,5-diphenyloxazole.