M-CSF was first characterized as a glycoprotein that induces monocyte and macrophage colony formation from precursors in murine bone marrow cultures. M-CSF binds CD14+ monocytes and promotes the survival/proliferation of peripheral blood monocytes.

M-CSF enhances inducible monocyte functions including phagocytic activity, microbial killing, and cytotoxicity for tumor cells as well as induces the synthesis of inflammatory cytokines such as IL-1, TNFα, and IFNγ in monocytes.

M-CSF binds to its receptor M-CSFR, and this receptor is shared by a second ligand, IL-34. Mouse M-CSF and IL-34 exhibit cross-species specificity, both bind to the human and mouse M-CSF receptors. IL-34 can regulate myeloid development and substitute for CSF-1 in vivo. IL-34 has overlapping but not identical biological activities as M-CSF.