In cells belonging to the myeloid cell lineages, four colonyinducing proteins were isolated (reviewed in refs. 24-30). The first colony-inducing factor identified was called mashran gmn from the Hebrew word meaning to send forth, with the initials for granulocytes and macrophages (31). This and other colony inducing proteins were then renamed with different names including macrophage/granulocyte inducers (16) and macrophage/granulocyte inducer type 1. They are now collectively called CSFs (reviewed in refs. 26 and 30), including one protein called interleukin 3 (IL-3) (20). Of these four CSFs, one (M-CSF) induces the development of clones with macrophages; another (G-CSF) clones with granulocytes; the third (GM-CSF) clones with granulocytes, macrophages, or both macrophages and granulocytes; and the fourth (IL-3) clones with macrophages, granulocytes, eosinophils, mast cells, erythroid cells, or megakaryocytes. The CSFs induce cell viability and cell multiplication (reviewed in refs. 26-29, 32, and 33) and enhance the functional activity of mature cells (reviewed in ref. 30). Cloning of genes from mice and humans for IL-3, GMCSF, M-CSF, and G-CSF has shown that these proteins are coded for by different genes (reviewed in ref. 34). Another cytokine identified more recently, stem cell factor (SCF) (35), has weak CSF activity and requires higher concentrations to induce colony formation. SCF induces colonies that contain myeloid cells in early stages of differentiation and can synergize with IL-3 and IL-6. The cytokines IL-3 and SCF appear to be capable of acting on more primitive myeloid precursor cells and to recruit them to respond to other CSFs. The ability of different CSFs to carry out similar and sometimes overlapping functions in the myeloid lineages demonstraites the flexibility of this multigene system. The receptors for M-CSF (c-fins) and SCF (c-kit) have a related intracellular tyrosine kinase domain (reviewed in ref. 36), whereas the receptors for GM-CSF, G-CSF, and IL-3, which do not have a tyrosine kinase domain, recruit src-related protein tyrosine kinases and the JAK2 protein tyrosine kinase to transmit their signals intracellularly (reviewed in ref. 37).