It is well known that the maintenance of oral hard and soft tissues is dependent on the presence of saliva since conditions negatively affecting salivary flow lead to rapid deterioration of oral health. This recognition of the importance of saliva has led to the structural and functional characterization of the major salivary proteins. Some of these proteins were found to exhibit strong antifungal activity in in vitro assays. While the total salivary antifungal activity is expected to be represented by the activities of all individual antifungal components, in vitro assays with total saliva show surprisingly little or no fungicidal activity. We have shown that saliva can be rendered active by lowering or removing its electrolytes making it possible to evaluate antifungal activities in the presence of all salivary proteins. It is well known that healthy individuals differ with respect to the carrier status of the oral opportunistic pathogen Candida albicans. Notably, every subject affected with oral candidiasis must have acquired carrier status before developing the disease. The focus of this application is based on the hypothesis that differences in salivary antifungal capacity between healthy individuals may explain differences in Candida carriage levels. To investigate this, it is planned to 1) assess the full extent of fungistatic and fungicidal activities of salivary secretions under native and desalted conditions, 2) investigate whether there is a relationship between whole saliva ionic strength or salivary antifungal capacity and oral yeast carriage, 3) initiate studies on the identification of components responsible for the activity of dialyzed parotid secretion. This project is the first step toward a more comprehensive investigation of the factors which promote host protection in a salivary environment. The experiments outlined here will provide the basis for a better understanding of antifungal mechanisms exerted by saliva in the oral cavity. ? ? ?