Epitope mapping shows that patients recovering from systemic infection with Candida albicans produce antibodies against both fungal-specific and conserved epitopes of the heat-shock protein (hsp) 90. In a mouse model of systemic candidosis, mortality was halved by prior administration of sera from two infected patients containing antibodies to hsp 90. One of these patients had no other candidal antibodies detectable on immunoblotting. The protective effect was mediated by the immunoglobulin fraction of the immune serum. It was not observed with a normal human serum. A mouse monoclonal antibody raised against one of the conserved peptide epitopes suggested that an autoantibody to hsp 90 could mediate protection against systemic candidosis in the animal model.