In this study, we investigated the effect of recombinant human interleukin-6 (IL-6) on colony-forming cells for granulocytes and macrophages (CFU-GM) cultured in suspension. IL-6 when used alone did not induce proliferation of highly purified CD34+ human hematopoietic progenitors. Moreover, no influence of IL-6 was observed on the proliferation induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte (G)-CSF. However, a marked survival enhancement (GM-CSF 228 +/- 42%, p < 0.01, and G-CSF 137 +/- 9%, p < 0.05) was observed when CD34+ cells were preincubated with IL-6 for 6 days. This survival effect became even more pronounced under serum-poor conditions (GM-CSF 380 +/- 80%, p < 0.01, and G-CSF 180 +/- 20%, p < 0.01) and could also be demonstrated at the single cell level in a colony-forming assay. By analysis of subpopulations of CD34+ bone marrow (BM) cells selected on the basis of CD45RO expression, the observed IL-6-mediated survival effect was found to be restricted to the CFU-GM containing CD45RO- subset. Our data show that IL-6 is a survival factor for CFU-GM.