The development of blood cells from hematopoietic stem cells is controlled by multiple cytokines. These growth factors influence survival, cell cycle status, differentiation into lineage-committed progenitors, final maturation into blood cells, and perhaps self-renewal of stem cells. The specific contribution of IL-6 to these processes in vivo was evaluated in mice with a targeted disruption of the IL-6 gene. Decreases in the absolute numbers of CFU-Sd12 and preCFU-S, as well as in the functionality of LTRSC in these mutant mice, suggests a role for IL-6 in the survival, self-renewal, or both of hematopoietic stem cells and early progenitors. In addition, as a result of the IL-6 deficiency, the control between proliferation and differentiation of the progenitor cells of the granulocytic-monocytic, megakaryocytic, and erythroid lineages into mature blood cells is altered, leading to abnormal levels of committed progenitors of these lineages and to a slow recovery from hematopoietic ablation.