CSF-1 regulation of macrophage development in the mouse and the effects of prolonged M279 anti–CSF-1R mAb treatment. HSCs give rise to common myeloid precursors, which generate monocyte-DC precursors that in steady state give rise to DC precursors and CSF-1R⁺Ly6C^hi and CSF-1R⁺Ly6C^lo monocytes. Monocytes enter the circulation from the marrow and are signaled to exit the blood to contribute to inflammatory processes (CSF-1R⁺Ly6C^hi) or to take up residence in specific locations (CSF-1R⁺Ly6C^lo). CSF-1 is a critical regulator of the differentiation, proliferation, and survival of CSF-1R⁺Ly6C^lo monocyte-derived tissue macrophages, alternatively activated macrophages, and tumor-associated macrophages. The cellular sources of CSF-1 are primarily mesenchymal in origin, but macrophages and tumors can also secrete this cytokine. Treatment with CSF1R blocking antibody M279 selectively depleted the CSF-1R⁺Ly6C^lo monocyte precursor of resident tissue macrophages, whereas CSF-1R⁺Ly6C^hi inflammatory monocytes were increased. Within tissue, the M279 mAb may prevent differentiation and proliferation of resident macrophage populations and tumor-associated macrophages.