Abstract Previous work has shown that in hybrid (BALB/cCr x DBA/2Cr)F1 mice the development of a fatal disseminated disease by systemic infection with virulent Candida albicans is associated with the detection of strong Th2-like responses. However, a predominant Th1-like response and long-lived antifungal protection are induced by vaccinating these mice with live blastospores of attenuated C. albicans strains. When injected into DBA/2Cr mice, one such live vaccine strain was found in the present study to result in a progressive disease characterized by strong Th2 responses. Elevated serum IgG1, IgA, and IgE responses, weak or absent footpad reactions, sustained production in vitro of Th2 (IL-4 and IL-10) but not Th1 (IL-2 and IFN-gamma) cytokines by CD4+ cells, and eosinophilia were all detected in DBA/2 mice after infection with the attenuated vaccine. This was in marked contrast with the development of strong Th1 responses and persistent anticandidal protection in similarly infected, H-2-compatible BALB/cCr mice. Therefore, our data suggest that the type of Th response that predominates in mice after C. albicans infection correlates with genetically determined susceptibility or vaccine-induced resistance. Moreover, the genetic control of this resistance may not be associated with the H-2 complex.