We investigated the effects of a protein-bound polysaccharide, PSK, on the resistance of tumor-bearing mice against Candida albicans infection. In BALB/c mice that had received subcutaneous (sc) transplantation of fibrosarcoma Meth A, viable fungal counts were increased in the kidney and the mean survival period was shortened after challenge with C. albicans, compared with healthy mice. Oral administration of PSK to such mice resulted in a significant decrease of viable fungal counts and a prolongation of the mean survival period. The ratio of CD4-positive T cells in the spleen was decreased in noninfected tumor-bearing mice and the decrease was prevented by PSK, although in vitro anticandida activities of phagocytes were not significantly affected by tumor burden or PSK. Further, intracellular interferon (IFN)-gamma productivity was enhanced and the number of IFN-gamma-producing CD4-positive T cells was enhanced by PSK. PSK enhanced the gene expression of interleukin (IL)-12 and IFN-gamma in the spleen of tumor-bearing mice inoculated with C. albicans. Treatments with anti-IL-12 or anti-IFN-gamma antibody reduced the anti-infectious effects of PSK. These findings suggest that the protective effect of PSK on sublethal inoculation with C. albicans in tumor-bearing mice is possibly mediated by Th1 cell functions.