Interleukin 6 (IL-6) refers to the gene product that was characterized initially as beta 2 interferon/26-kDa protein produced by human fibroblasts and later was found to be identical to B-cell stimulatory factor 2, hybridoma/plasmacytoma growth factor, and probably hepatocyte-stimulating factor. Using the human IL-6 cDNA as a probe, we have isolated functional cDNA clones from mouse bone marrow stromal cell cDNA libraries. Sequence analysis of the mouse cDNA insert revealed significant homology between the human and mouse IL-6 cDNA clones both at the level of nucleotide (65%) and deduced amino acid (41%) sequences. The NH2-terminal sequence of the deduced protein is identical to a partial NH2-terminal sequence determined previously for a hybridoma/plasmacytoma growth factor and a plasmacytoma growth factor isolated from mouse T cells and macrophages, respectively. The mRNA for mouse IL-6 is expressed in IL-1-treated stromal cells and in activated T-cell and macrophage cell lines. Supernatants from COS-7 monkey cells transfected with the cDNA clone have plasmacytoma growth factor, hepatocyte-stimulating factor, and colony-stimulating factor activities, as well as the ability to support the growth of a factor-dependent myeloid cell line, thus revealing an additional biological activity for IL-6.