The aim of the present study was to investigate the contribution of granulocytes and monocytes to resistance against an acute systemic candidal infection in mice. To this end granulocytopenia and monocytopenia were induced by irradiation or treatment with cyclophosphamide, and monocytopenia was obtained by treatment with VP-16. After intravenous injection of 1×10⁴ Candida albicans into mice irradiated with 8 GY, the number ofCandida albicans cultured from the kidneys, expressed as the geometric mean of the number of CFU/g tissue, was 5.4×10⁴, 7.1×10⁶ and 5.8×10⁷ on days 1, 3 and 5 of infection respectively (p<0.001 compared to normal mice). The number ofCandida albicans cultured from the liver and spleen was also significantly higher for irradiated animals than for normal mice (p<0.001). For cyclophosphamide-treated mice the number of organisms in the kidney (1.7×10⁴ CFU/g on day 1, 1.9×10⁶ on day 3 and 3.8×10⁶ on day 5 of infection) and spleen was significantly higher (p at least <0.02) than for nomal mice after injection of 1×10³ Candida albicans. Monocytopenia induced by VP-16 did not result in an increase in the number ofCandida albicans cultured from the kidney or spleen after infection. From these studies it is concluded that granulocytes and not monocytes or exudate macrophages play an important role in resistance againstCandida albicans during the first five days of a systemic infection.