We examined the effects of co-administration of recombinant human (rh) IL-6 (10 micrograms/day) and rh granulocyte colony-stimulating factor (G-CSF) (0.35 micrograms/day) on the number of peripheral blood cells and peripheral progenitor cells in mice. Among blood cells counts, only white blood cells were synergistically enhanced by co-administration of rhIL-6 and rhG-CSF. Moreover, it was found that co-administration of rhIL-6 and rhG-CSF also caused a marked synergistic increase in the number of peripheral blood progenitor cells. Namely, in combination with rhG-CSF, which alone induced a 170-fold increase in peripheral granulocyte-macrophage colony-forming units (CFU-GM) on day 14, rhIL-6 synergistically increased the number of CFU-GM to more than 1600-fold higher than the number in control mice. Administration of rhIL-6 alone induced a 46-fold increase in CFU-GM. Similar synergistic increases of other hematopoietic progenitors, such as colony-forming units in spleen and megakaryocyte colony-forming units in blood, were also observed in mice co-administered rhIL-6 and rhG-CSF. The survival rate of lethally irradiated recipient mice transplanted with mononuclear cells from 100 microliters of blood from mice administered rhIL-6 and/or rhG-CSF was examined. When mononuclear cells from mice co-administered rhIL-6 and rhG-CSF were injected, survival rate at day 100 was 92%. In contrast, recipient mice transplanted with mononuclear cells from mice administered either rhIL-6 or rhG-CSF alone showed a survival rate of 31% or 46%, respectively, although transplantation of mononuclear cells from control mice failed to rescue any lethally irradiated recipient mice. These results suggest that co-administration of rhIL-6 and rhG-CSF may be useful for peripheral blood stem cell transplantation.