Interleukin-6 (Il-6), also known as B cell stimulatory factor 2/interferon beta 2, has been found to support colony formation by murine granulocyte-macrophage progenitors. We have reported that Il-6 also acts synergistically with interleukin-3 (Il-3) in the support of the proliferation of multipotential stem cells in the quiescent, Go phase of the cell cycle. Our serial observations (mapping studies) of the development of blast cell colonies from spleen cells harvested from mice 4 days after the injection of 150 mg/kg 5-fluorouracil revealed that the blast cell colonies appeared earlier in culture in the presence of Il-6 and Il-3 than with either factor alone. Because the combination of factors did not alter the rate of growth of the colony, this effect must result from an early exit from Go. In the human system using purified, My-10+ bone marrow progenitors in a culture system with delayed addition of growth factors, the combination of Il-6 and Il-3 yielded twice as many colonies as did Il-3 alone. The human blast cell colonies also appeared at earlier times when grown in the presence of Il-6 and Il-3 as compared to either factor alone. These results suggested that human Il-6 acts synergistically with Il-3 in the support of the proliferation of human and murine hemopoietic stem cells in Go and that part of the effect appears to be a shortening of the Go residence time of the hemopoietic stem cells.