The role of serum factors in the modulation of production of colony-stimulating activity (CSA) has been investigated. A factor has been described, and partially characterized, in human serum that has the capacity to stimulate increased synthesis and release of CSA by human mononuclear cells (MNC). MNC RNA and protein synthesis are required to demonstrate this effect of serum, but DNA synthesis and mitotic division are not required. The factor in serum resulting in this effect is a heat-labile protein with a molecular weight slightly greater than that of CSA.