M-CSF is a hematopoietic growth factor that stimulates the proliferaion and differentiation of mononuclear progenitors into mature cells and promotes the production of other cytokines. There are an increasing number of reports describing the in vitro or in vivo antifungal effect of M-CSF. The present study was designed to investigate the effect of rhM-CSF expressed in silkworm on chemotherapeutically treated mice with invasive fungal disease. 200 mg/kg cyclophosphamide (CY) was injected (ip) into mice to make the model of chemotherapeutically lesions. Four days after CY injection the mice were infected (iv) with C. albicans (2 x 104cells per mouse) and were administered differtdoses of rhM-CSF, alone in combination with fluconazole (300 ug/ kg), once a day for 6 days. The number of survival animals in each group was determined every day until the end of the 3-week experimental period. Survival rates and medial survival time were evaluated by SPSS. The results demonstrate that combination therapy with rhM-CSF and FLCZ showed higher survival rate more than in the therapy with either rhM-CSF or FLCZ alone. When 250 ug/kg rhM-CSF treatment was combined with FLCZ, the survival rate over a 3-week period reached 50.0% (cf. survival rates of 28.6% for FLCZ alone and 35.7% for hM-CSF alone) and median liter of C. albicans culture from the kidneys were greatly decreased relative to the control. These results indicate that rhM-CSF expressed in silkworm could effectively improve the survival rate and medial survival times of chemotherapeutically treated mice with invasive fungal disease.