The effect of recombinant granulocyte colony-stimulating factor (rG-CSF) on acute disseminated Candida albicans infection in nonneutropenic mice was investigated. Mice treated with a single dose of rG-CSF showed a significantly reduced mortality (28% vs. 90%; P < .001). The outgrowth of C. albicans from the kidneys, spleens, and livers of rG-CSF-treated mice was significantly reduced (log cfu/g of kidney, 5.54 vs. 7.13; P < .001), as were circulating tumor necrosis factor-alpha and interleukin-1beta. After rG-CSF, the kidneys showed fewer infectious infiltrates, enhanced granulocyte influx, and almost complete absence of hyphal outgrowth. During peritoneal C. albicans infection, rG-CSF enhanced influx of granulocytes to the site of infection, and exudate granulocytes showed increased oxygen radical production. These results indicate that rG-CSF enhances host resistance to disseminated candidiasis in nonneutropenic mice through activation of granulocytes and their recruitment to the site of infection.