My colleagues and I previously found a subset of neutrophil-like Ly6C hi monocytes, named "regulatory monocytes", that expand in the bone marrow during the late phase of inflammation. Regulatory monocytes migrate to injured tissue where they promote tissue repair. Unlike classical Ly6C hi monocytes, regulatory monocytes arise from GMP through proNeu1, which was previously thought to be committed to becoming neutrophils. G-CSF not only stimulates neutrophil differentiation but also drives the expansion of regulatory monocytes in the absence of inflammatory stimuli. The human parallel to mouse regulatory monocytes was found in the peripheral blood CD14 hi CD16 lo monocyte fraction. These monocytes can be distinguished from classical CD14 hi CD16 lo monocytes by neutrophil marker CXCR1 expression. Like mouse regulatory monocytes, human CXCR1 + monocytes arise from neutrophil progenitors in response to G-CSF. CXCR1 + CD14 hi CD16 lo monocytes suppressed the proliferation of syngeneic T cells in vitro, which suggests an immunosuppressive phenotype. Overall, these findings indicate that the process of differentiation of regulatory monocytes from progenitors of neutrophil lineage is maintained across humans and mice, and may aid in resolution of excess inflammation.