A murine model of candidiasis, involving the induction of immunity by cutaneous inoculation of viable Candida albicans blastospores, was used to investigate the nature of protective immune mechanisms as well as the potential immunoregulatory influences of antigen on the development of previously defined immune responses. Two approaches were used to attempt to define the mechanism of protective immunity, viz., immune responses in the partially B-cell deficient CBA/N mouse strain were compared to those in the immunocompetent CBA/J strain, and a cutaneous transfer model was developed in C57BL/6 mice involving the transfer of lymphoid cells or serum in combination with viable C. albicans. CBA/N mice responded immunologically to C. albicans in the same manner as CBA/J mice, indicating that the development of immune responses, e.g. delayed hypersensitivity demonstrable in vivo and in vitro, Candida-specific antibody, and the ability to resist reinfection, was not influenced by the immune defect present in CBA/N mice. In the transfer model, which involved the quantitative culture of lesions resulting from the cutaneous inoculation of viable C. albicans combined with lymphoid cells and serum, the presence of serum with antibodies specific for cytoplasmic or cell wall antigens had no influence on the killing of blastospores within the lesion, but lymphoid cells from immune animals were effective anti-Candida agents. Moreover, the candidastatic activity of the transferred lymphoid cells could be ablated by prior treatment of the cells with surface-antigen specific antisera, indicating a Thy-1.2('+), Lyt-1('+), I-A('-) phenotype for the cells responsible for inhibiting candidal growth in situ The immunoregulatory aspects of circulating antigen were investigated by intravenous pretreatment of BALB/c or CBA/J mice with two cell wall antigens or heat-killed C. albicans prior to immunization and measurement of immune responses. Mice pretreated with one of the cell wall antigens, the glycoprotein, were suppressed in their responses to that antigen, but not to other Candida antigens, and failed to develop a protective response demonstrable in the brain. Cell wall mannan and heat-killed blastospores were not immunosuppressive in this model