We induced resistance to systemic Candida albicans infection through CD4⁺-cell-mediated immunity in mice by immunization with subcutaneous injections of live C. albicans cells emulsified in incomplete Freund adjuvant. Using the resistant mice, we tested subcellular fractions of C. albicans cells for antigenicity. The fractions were derived from digested surface cell walls, insoluble membranes, or soluble and insoluble cytoplasmic materials, which were prepared by treatment with cell wall-digesting enzymes followed by lysis of the consequent protoplasts. Interestingly, the live-cell-immunized mice showed strong cell-mediated immune responses to the membrane fraction (C. albicans membrane antigen [CMA]). In addition, immunization with CMA induced resistance to systemic candidiasis, which disappeared upon administration of anti-CD4 monoclonal antibody. Infusion of splenocytes from the CMA-immunized mice conferred resistance on SCID mice, whereas infusion of CD4⁺-T-cell-depleted splenocytes was unable to induce resistance, indicating the importance of CD4⁺ lymphocytes for resistance. These results suggest a potential for the membrane fraction to act as an antigen conferring resistance to systemic candidiasis in place of live cells and also as a source for the isolation of a new antigen.