Candida species activate complement by the alternative pathway, induce leukocyte migration and, when applied epicutaneously, cause epidermal microabscesses of neutrophils in man and experimental animals. Complement activation by C. albicans appears to be a property of the cell wall. To biochemically identify the complement-activating constituent(s) of C. albicans, an ethyleneglycol extract of growth phase blastospores was prepared. Acid hydrolysis and neutral sugar analysis revealed mannose (82%), fucose (7%), and glucose (11%). The soluble, mannose-rich cell wall polysaccharide of C. albicans activates serum complement via the alternative pathway, induces neutrophil chemotaxis and is antigenically reactive with antisera to C. albicans. This constituent exhibits in vitro endotoxin-like activity as measured by Limulus lysate gelation, but is nonpyrogenic in rabbits. The extracts produced precipitin lines in double immunodiffusion studies against serum from patients with invasive candidiasis and rabbit antisera to mycelial and blastospore preparations of C. albicans, but not against normal serum. Thus, pathogenic properties and reactive phenomenon of C. albicans are in part attributable to a cell wall polysaccharide, mannan.