Glucan, a potent reticuloendothelial stimulant, is a glucopyranose polysaccharide derived from zymosan. Because of glucan's potential as an immunotherapeutic agent, we performed studies in order to determine its effect on granulopoiesis and macrophage production in mice. One week after the i.p. injection of 4 mg of glucan, there was a tenfold increase in colony-forming cells in the spleen and approximately a twofold increment of cells in the bone marrow and the peritoneal cavity capable of colony formation in vitro. There was a relative and absolute increase in the number of pure macrophage colonies from bone marrow and spleen. The total macrophage content in spleen, peritoneal cavity, and bone marrow as also increased in the treated mice. Serum from glucan-injected mice had high colony-stimulating activity levels, and the peritoneal macrophages elaborated increased colony-stimulating activity in vitro as compared to controls. Peripheral white blood cell counts were two times greater than those of control in the glucan-treated mice. These studies indicate that glucan administration results in increased granulocyte and macrophage production. The enhanced leukopoiesis is probably mediated in part by augmented release of colony-stimulating activity from macrophages. These observations suggest that the use of glucan as an immunotherapeutic agent can result in an increased number of available effector cells.