Ovine/Caprine Macrophage Colony-Stimulating Factor (M-CSF) is a cytokine that regulates the development, proliferation, and survival of monocytes and macrophages in sheep (Ovis aries) and goats (Capra hircus). The M-CSF protein is identical at the amino acid level in these two species, reflecting strong evolutionary conservation of this key regulator of macrophage biology in small ruminants. M-CSF is produced by several cell types, including fibroblasts, endothelial cells, epithelial cells, and stromal cells, in response to tissue signals and inflammatory stimuli. Ovine and caprine M-CSF bind to the colony-stimulating factor-1 receptor (CSF1R), a receptor tyrosine kinase expressed on monocytes and macrophage lineage cells, activating intracellular signaling pathways such as PI3K–AKT, ERK/MAPK, and JAK–STAT that promote differentiation and maintenance of macrophage populations. Through these mechanisms, M-CSF supports macrophage-mediated immune surveillance, phagocytosis, tissue homeostasis, and inflammatory responses. Because macrophages play a central role in host defense, M-CSF–mediated macrophage function is important for maintaining immune health and resistance to infection in sheep and goats. In cell culture, recombinant ovine/caprine M-CSF is commonly used to promote differentiation of monocytes or bone marrow–derived cells into macrophages and to support macrophage proliferation and functional assays in vitro. Ovine and caprine M-CSF are also studied in animal model and veterinary research, including investigations of macrophage responses to pathogens such as Mycobacterium avium subsp. paratuberculosis and small ruminant lentiviruses.