Two different strains of mice with different susceptibilities to systemic candidiasis (BALB/c and CBA/H) were infected with Candida albicans SC5314. Immune sera were obtained on different days post-infection and assayed against two-dimensional polyacrylamide gel electrophoresis separation of cytoplasmic extracts obtained from protoplasts. More than 31 immunoreactive proteins were detected. Some of them were identified and found to correspond to (i) glycolytic enzymes, such as fructose biphosphate aldolase, triose phosphate isomerase (TPIS), glyceraldehyde-3-phosphate dehydrogenase, 3-phosphoglycerate kinase (PGK), enolase (ENO1) and pyruvate kinase, (ii) other metabolic enzymes, such as methionine synthase (METE), inosine-5'-monophosphate dehydrogenase (IMH3), alcohol dehydrogenase and aconitate hydratase and (iii) heat shock proteins: HS71 (or Ssa1p) and HS75 (or Ssb1p), both from the HSP70 family. This work reports for the first time antigenic properties for IMH3 and TPIS. Different profiles of antibody expression, depending on the mouse strain and the course of infection, were observed. ENO1 was the most immunogenic protein in infected BALB/c mice (the most resistant strain). On the other hand, sera from CBA/H mice (a more susceptible strain) showed a strong increase in reactivity along the infection against METE, HS75 and PGK. Many of these immunoreactive proteins have also been detected using sera from human patients with systemic candidiasis, thus indicating the usefulness of the murine model for studying the antibody response in systemic candidiasis. In this work we demonstrate that the combination of two-dimensional electrophoresis with immunoblotting using murine immune sera can be an important tool for the identification of C. albicans antigens and for monitoring the evolution of the disease.