We studied the long-term in vivo effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) on in vitro growth of granulocyte/macrophage colony forming cells (GM-CFC) in bone marrow and peripheral blood obtained from two patients with autoimmune neutropenia, who received rhG-CSF. Along with rhG-CSF treatment for more than 40 d, numbers of GM-CFC-derived colonies from both bone marrow and peripheral blood gradually decreased to a significant level though white blood cells in peripheral blood and nucleated cells in bone marrow were increased in number. This observation suggests that long-term administration of rhG-CSF may preferentially activate a differentiation pathway for granulopoiesis while proliferation of GM-CFC is not induced as expected in response to rhG-CSF.