Inbred mice can be classified as susceptible or resistant to systemic infection with the yeast Candida albicans by histopathological evaluation of tissue lesions. Candida-specific memory T cell responses generated by resistant BALB/c mice are vigorous and sustained, whereas those displayed by susceptible CBA/H mice are weak. When spleen cells from immune mice were activated by culture with candida antigens in vitro, and injected into syngeneic and allogeneic recipients in the absence of further antigenic stimulation, cells from CBA/H mice induced a specific inflammatory response only in CBA/H recipients. In contrast, cells from immune BALB/c mice showed no specific activity. The effector cells were identified as T cells of the cytotoxic/suppressor subclass (CD4-, CD8+); and analysis in various F1 hybrid mice showed that reactivity was expressed only in animals carrying CBA/H genes. The data thus indicate that susceptibility to C. albicans infection is associated with the induction of a T cell subpopulation that has the potential to react specifically against unmodified self antigens expressed by the susceptible strain.