The rather narrow variation in the number of mononuclear phagocytes in blood and tissues under steady-state conditions attests to a fine tuning mechanism regulating monocyte production and distribution. Some factors, such as CSF, prostaglandins, and lactoferrin, which are thought on the basis of in vitro findings to control homeostasis of the mononuclear phagocyte system, are reviewed, confirmation of the physiologic role of these factors will require in vivo studies. Under conditions leading to an increased demand for macrophages in tissues, large numbers of monocytes are produced in the bone marrow. Two endogenous factors, i.e. the factor increasing monocytopoiesis (FIM) and the monocyte production inhibitor (MPI), have been found to regulate monocytopoiesis in vivo during an inflammation. FIM occurring in the circulation during the initial phase of the inflammatory reaction is a protein that has no colony-stimulating activity, is cell-line specific, and stimulates the mitotic activity of the promonocytes and probably also the proliferation of the monoblasts. Macrophages produce and secrete FIM. MPI occurs in the circulation during the second phase of an inflammation. Although with the present assays these factors are only demonstrable during inflammation, which indicates that FIM and MPI are regulators of monocytopoiesis under increased demand, their possible role in control of homeostasis under normal steady-state conditions is not yet clear.