Granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor, is a clinically effective drug used to promote neutrophil recovery in patients with chemo- or radiotherapy-induced neutropenia. We have reviewed the pharmacokinetic and pharmacodynamic properties of three kinds of G-CSFs: E. coli derived G-CSF, CHO-derived G-CSF, and mutein G-CSF. The clearances of G-CSFs are saturable and autoinducible in experimental animals and humans. That is, the systemic clearances of G-CSFs decrease as the dose injected increases and approaches a constant value. Both saturable and nonsaturable processes are involved in G-CSF elimination. Also, the systemic clearances of G-CSFs are increased by repeated administration of G-CSF. Although the relative bioavailability of G-CSFs after subcutaneous administration is approximately 60%, the increase in peripheral white blood cells or neutrophils is greater than that after intravenous administration at the same dose. The effects of G-CSFs seem to be time dependent rather than AUC dependent, considering that mean residence time of G-CSFs in the plasma is longer after subcutaneous administration than that after intravenous administration. There is a slight difference in the pharmacokinetics of E-coli- and CHO-G-CSF although they seem to be pharmacologically equivalent. The correlation between G-CSF clearance and peripheral neutrophil counts in the patients suggests that G-CSF receptors contribute to G-CSF clearance. Quantitative pharmacokinetic analysis using mutein G-CSF shows that the G-CSF receptor plays a major role in saturable G-CSF clearance, and that this saturable process accounts for approximately 80% of the total clearance at low doses. That is, the degradation following the receptor-mediated endocytosis in bone marrow might be a major clearance system of G-CSF at a physiological blood level. The G-CSF receptor in bone marrow might work not only as a signal transducer for differentiation and proliferation of granulopoietic precurcer cells but as a regulator of G-CSF levels in blood. In addition, at high doses, glomerular filtration in the kidneys is the major process for nonsaturable G-CSF clearance. At present, polyethylene glycol derivatives of G-CSF are being developed to reduce the frequency of G-CSF administration.