Daucosterol is a natural phytosterol-like compound. It is the glucoside of β-sitosterol. Direct interaction of daucosterol with C. albicans yeast cells resulted in no growth-inhibition by in vitro susceptibility analysis. In contrast, mice given daucosterol (DS) intraperitoneally before intravenous challenge with live C. albicans yeast cells survived longer than DS-untreated control mice against disseminated candidiasis (P<0.05). By assessment of the fungal CFU in kidneys, DS-treated mice before the challenge developed about 81% fewer kidney CFU than untreated controls. This protection was removable by pretreatment of mice with anti-CD4+ antibody before the DS-treatment and challenge with the yeast. By treatment of DS-given mice with anti-mouse IFNgamma, the protection was also abolished. DS protects mice against disseminated candidiasis by the CD4+ Th1 immune response.