The protective role of humoral antibodies in the resolution of systemic candidiasis remains controversial. Investigation of the humoral immune responses in mouse strains of varying susceptibility to infection may demonstrate a link between mouse strain susceptibility, antibody production and specificity, and the ability to resolve an infection. The antibody response in five different strains of mice during primary immune response to systemic infection with Candida albicans was investigated. Immune sera were fractionated by protein A affinity chromatography to yield fractions containing IgG1, IgG2a and IgG2b immunoglobulins. BALB/c mice of low susceptibility to the infection and DBA/2J mice of high susceptibility produced increased levels of the IgG1 isotype and decreased levels of the IgG2a isotype. AKR, CBA/H and C57B1/6J mice of moderate susceptibility produced antibodies predominantly of the IgG2a isotype. The patterns of antigen recognition by antibodies in immune sera and in fractions obtained after protein A chromatography of immune sera were investigated by western blotting and immunostaining. Antibodies from AKR(H-2K) and CBA/H (H-2k) mice reacted strongly after immunoblotting with antigens of 87 and 96 kDa. In contrast, immune sera from both the highly susceptible DBA/2J (H-2d) mice and the resistant BALB/c (H-2d) mice reacted strongly with an antigen of 48 kDa. C57B1/6J (H-2b) mice produced variable antibody reactivity to antigens of 48, 65, 66 and 79 kDa depending on the IgG subclass tested. The IgG subclass responses and the patterns of antigen recognition in these mice suggest that humoral responses to C. albicans may be restricted by H-2 haplotype.(ABSTRACT TRUNCATED AT 250 WORDS)