Immune responses to defined antigens of the AIDS opportunistic pathogen Candida albicans that arise as a consequence of alimentary tract colonization or induced candidemia were assessed. Lymphocyte activation and antibody production to the abundant immunodominant antigen enolase were evident in germfree mice colonized with C. albicans. Lymphocytes from colonized or intravenously challenged mice responded to a recombinant C. albicans enolase fusion protein (EFP). The responses to EFP were significantly higher than the responses to a control protein, glutathione S-transferase. In immunoblotting experiments, enolase was the immunodominant humoral immunogen in these mice. These results demonstrate that enolase stimulates cellular and humoral responses and that specific immune responses to enolase are sensitive indicators of the presence of proliferating C. albicans in mice.