To study the regulation of granulopoiesis, we measured the effect of endotoxin on peripheral leukocyte counts and on colony-stimulating factor (CSF) in the serum of CF1 mice. The peripheral granulocyte level fell from 612 ± 69 (mean ± S.E.M.) to 147 ± 20 per cubic millimeter within 45 minutes of intraperitoneal injection of 5 μg of Salmonella typhosa endotoxin. In control animals, the CSF in 0.1 ml of serum stimulated the growth of 0.56 ± 0.4 in vitro myeloid colonies per 105 cells. Forty-five minutes after endotoxin the CSF activity had increased to 7.7 ± 6.1 colonies per 105 cells; after two hours it was 29.6 ± 10 colonies per 105 cells. Six hours after endotoxin the marrow was depleted of polymorphonuclear cells. Thereafter, sequential increases in the myeloblast-promyelocyte and myelocyte compartments of the marrow at 24 to 48 hours, respectively, suggested a wave of differentiation from a precursor compartment with subsequent maturation. The data suggest that intermittent endotoxemia may be one determinant of serum CSF levels, which, in turn, may play a part in regulating granulopoiesis.