Mannan-binding lectin (MBL) is a component of the innate immune system. The goal of the present study was to evaluate binding of MBL to Candida albicans in vitro and in vivo and to assess the impact of MBL treatment on host resistance. The results showed a variable and often discontinuous pattern of binding to individual yeast cells. MBL bound to cells grown at 37 degrees C but not to cells grown at 23 degrees C. The putative MBL ligand was constitutively present on yeast cells grown at 23 degrees C, but the ligand was masked on such cells, such that MBL could not bind. C. albicans yeasts and hyphae in infected tissue bound MBL. Finally, parenteral administration of MBL increased resistance of mice to hematogenously disseminated candidiasis. These results suggest that MBL is an important component of innate resistance to candidiasis and that MBL therapy may be a means to prevent disseminated candidiasis in high-risk patients.