A factor increasing monocytopoiesis (FIM) has been demonstrated during the onset of an acute inflammatory reaction caused by an intraperitoneal injection of polystyrene latex particles. It is protein in nature, does not contain a carbohydrate moiety essential for its function, and is very probably not a glycoprotein. The molecular weight of FIM lies between 18,000 and 24,000 daltons (determined with both ultrafiltration membranes and gel filtration on Sephadex G100). The monocytosis induced by FIM is dose dependent. FIM is thermolabile, having a half-time of about 20 min at 37 degrees C in serum; temperature inactivation can be delayed by the addition of epsilon- aminocaproic acid, the half-time at 37 degrees C then being about 45 min. In vitro treatment of normal murine blood with the inducers of the inflammatory reaction does not result in FIM activity in the serum. FIM dose not have chemotactic activity toward macrophages, is not a clotting factor, is not a biologically active fragment of the complement system, and has no colony-stimulating or-enhancing activity in the vitro bone marrow colony assay. On the basis of these results, a mechanism is postulated for the humoral regulation of monocytopoiesis.