We studied the ability of the human hemopoietic growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) to activate polymorphonuclear neutrophils (PMN) for increased phagocytosis of opsonized Candida albicans and enhanced degranulation. Exposure of neutrophils to these two growth factors resulted in an increased number of Candida phagocytosed. Pretreatment of the neutrophils with the monoclonal antibody anti-Mol abrogated the enhanced phagocytosis associated with GM-CSF priming but not that of G-CSF primed PMN. In examining the effect of these two colony-stimulating factors (CSFs) on neutrophil degranulation we found that GM-CSF induced enhanced release of lysozyme from cytochalasin-treated PMN in the presence of Candida; however, G-CSF did not. The effect of GM-CSF on lysozyme release was abrogated by anti-Mol antibody. These data suggest that GM-CSF and G-CSF prime PMN for certain enhanced functional activities by distinct mechanisms. The differential effect of the CSFs on neutrophil degranulation may relate to the more common inflammatory symptoms seen when GM-CSF is used clinically as compared to the experience with G-CSF.