Hemopoietic negative regulators are growth inhibitory proteins or peptides of natural origin that exert their effects on cells of the blood-forming system. They are biologically defined by quantitative assay methods that exclude toxicity as a basis for their action. They act within minutes to hours, in a readily reversible and more-or-less specific manner on stem cells and progenitor cells, during S-phase to arrest DNA synthesis, or during G1 to prevent entry into DNA synthesis. Operating at picomolar to nanomolar concentrations through high-affinity receptors at their target cell surface, they oppose the action of stimulatory (or positive regulatory) growth factors. Hemopoietic negative and positive regulators acting in concert thus appear to provide a mechanism for rapid, reversible, and specific proliferative responses to changes in hemopoietic demand.