Extracellular proteolytic activity of the human pathogen Candida albicans is due to the activity of at least nine secreted aspartyl proteinase (Sap) isoenzymes. SAP1-9 genes are differentially regulated both in vitro and in vivo at the transcriptional level. All SAP genes are translated into preproenzymes, which are processed by a signal peptidase and a Kex2-like proteinase. In vitro experiments using purified Saps suggested that active Saps may play a role in attachment, colonization, penetration of host tissues and immune evasion. In vivo expression of SAP1-6 during oral candidosis was established. Using sap mutants, produced by targeted gene disruption, a prominent role for SAP1-6 during murine disseminated infections and for SAP1-3 during rat vaginal infections could be demonstrated. These data underline the general importance of extracellular proteinases for the pathogenesis in C. albicans infections.