We examined the effect of human recombinant (r) interleukin 6 (IL-6) on the differentiation of murine and human hemopoietic progenitors. Human IL-6 supported colony formation by murine bone marrow cells. These colonies consisted of neutrophils and macrophages. Recombinant IL-6 was able to support multilineage colony formation by spleen cells from 5-fluorouracil (5-FU)-treated mice. These colonies consisted of greater than 1 x 10(4) cells. Differential counts revealed large colonies exhibiting different combinations of cell lineages: neutrophils, macrophages, eosinophils, mast cells, and megakaryocytes. However, when blast cell colonies supported by interleukin 3 were replated into secondary dishes containing IL-6, they could differentiate into only neutrophils and macrophages. Single cells transferred from blast cell colonies formed only neutrophil/macrophage colonies. These results indicate that IL-6 had a direct effect on the growth and development of murine granulocyte-macrophage progenitors at a late stage and a significant effect on multipotential hemopoietic precursors that might be indirect through other cells. By contrast, human rIL-6 did not support colony formation by human bone marrow mononuclear cells. IL-6 may not show an independent activity for human hemopoiesis of myeloid lineage. However, the synergistic activity of IL-6 remains to be clarified.