OBJECTIVE Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now widely used in normal donors for collection of peripheral blood progenitor cells for allogeneic transplantation and granulocytes for transfusion. Currently available data on biologic and molecular effects, and safety of rhG-CSF in normal healthy volunteers are reviewed. RESULTS In addition to its known activating role on neutrophil kinetics and functional status, rhG-CSF administration can affect monocytes, lymphocytes and the hemostatic system. Granulocyte colony-stimulating factor receptors were identified in a variety of nonmyeloid tissues, although their role and functional activity have not always been well defined. Moreover, rhG-CSF is capable of modulating complex cytokine networks and can impact the inflammatory response. In addition to its known mobilizing role for peripheral blood progenitor cells, rhG-CSF can mobilize dendritic and endothelial progenitor cells as well. On a clinical level, serious rhG-CSF-related adverse events are well described (e.g. splenic rupture) but remain rare. CONCLUSIONS rhG-CSF effects in healthy volunteers, although normally transient and self-limiting, are now believed to be more complex and heterogeneous than previously thought. Although rhG-CSF administration to healthy volunteers continues to have a favorable risk-benefit profile, these new findings have implications for safeguarding the safety of normal individuals.