Neutropenia often accompanies septicemia in burned patients. This paradox suggests a defect in the regulation of granulopoiesis. Colony stimulating factor (CSF) produced by the monocyte-macrophage system is an important regulator of granulocyte production. We followed serial serum CSF levels and peripheral blood leukocyte differential counts in 22 patients with >30% burns. Six patients (mean burn, 58%) developed Gram-negative septicemia and died (Group I). Sixteen patients (mean burn, 38%) had no fatal septicemias (Group II). Nonsurvivors had initially low levels of CSF and developed persistent monocytopenia. Survivors, in contrast, had prompt rises in CSF and developed monocytosis. The presence of monocytopenia and low CSF levels in Group I suggests an abnormality in the stimulatory arm regulating granulopoiesis. Such a defect may play a role in the development of fatal septicemia following severe thermal injury.