THE haemopoietic system has three main compartments: multi-potential stem cells, intermediate stage progenitor cells and mature cells. The availability of simple reproducible culture systems¹ has made possible the characterization and purification of regulators of the progenitor cells, including colony-stimulating factors and interleukins. In contrast, our knowledge of the regulators involved in the control of stem cell proliferation is limited. The steady-state quiescent status of the haemopoietic stem cell compartment is thought to be controlled by locally acting regulatory elements present in the stromal microenvironment², but their purification has been hampered by the lack of suitable culture systems. We have recently developed a novel in vitro colony assay that detects a primitive cell (CPU-A) ³ which has similar proliferative charac-teristics, in normal and regenerating bone marrow, to the CFU-S (haemopoietic stem cells, as defined by the spleen colony assay⁴) and which responds to CFU-S-specific proliferation regulators. We have now used this assay to purify to homogeneity a macrophage-derived reversible inhibitor of haemopoietic stem cell proliferation (stem cell inhibitor, SCI). Antibody inhibition and sequence data indicate that SCI is identical to a previously described cytokine, macrophage inflammatory protein-lα ( MIP-lα), and that SCI/MIP-lα is functionally and antigenically iden-tical to the CFU-S inhibitory activity obtained from primary cultures of normal bone marrow cells⁵. The biological activities of SCI/MIP-lα suggest that it is a primary negative regulator of stem cell proliferation and that it has important therapeutic appli-cations in protecting haemopoietic stem cells from damage during cytotoxic therapies for cancer.