The elaboration of extracellular proteolytic activity by Candida albicans during growth in laboratory broth or in human whole salivary supernatant was investigated. Growth of the organism in broth at pH 3 to 7 followed by assay of culture supernatants at pH 4 (optimum for activity) indicated protease was only present in cultures grown at a pH of less than 5. In contrast, growth in sterile human whole salivary supernatant over the pH range of 3 to 7 uniformly failed to result in production of protease. Growth of the organism at pH 4 in broth supplemented with saliva resulted in a saliva-dependent inhibition of protease production. Although the addition of up to 16% (vol/vol) saliva had essentially no effect on growth, 4% saliva caused a 50% reduction in proteolysis of substrate protein. Due to the low pH requirement for protease production and activity and the demonstration that saliva is a potent inhibitor of protease synthesis, we conclude C. albicans most likely does not produce extracellular protease in the human oral cavity.