The limiting factors for the generation of the bacterial inhibitor, hypothiocyanite OSCN- ion, in human whole saliva were studied. Significant increase in OSCN- production could be achieved both in vitro and in vivo by supplementing saliva with peroxide alone or with a combination of peroxide and SCN-. The most effective initial H2O2 concentration was 700 μM. Higher concentrations caused a rapid loss in the amount of OSCN-. In contrast to expectations, supplementation of saliva with excess lactoperoxidase resulted in decreased generation of OSCN- ions. From these results we conclude that the enhancement of this naturally occurring antimicrobial system is possible by a combination of peroxide and SCN- ions added to human saliva in the appropriate ratios.