Oxidation of glucose, utilization of oxygen, and reduction of nitroblue tetrazolium (NBT) were determined in human toxic neutrophils. Leukocytes from healthy volunteers and from patients with febrile illnesses unassociated with toxic neutrophils served as controls. Oxygen utilization and hexose-monophosphate-shunt activity (HMS) were variable in toxic neutrophils; however, the mean levels of oxygen utilization and HMS activity were slightly elevated in toxic neutrophils following phagocytosis of latex particles. No alteration in quantitative reduction of NBT dye was detected in toxic neutrophils, but the histochemical reduction of NBT dye was significantly increased in these cells. The metabolic perturbations of toxic neutrophils could not be attributed to the degree of leukocytosis, cellular immaturity based on nuclear configuration, the presence of fever, azotemia, hypotension, or antibiotic therapy. Sera from patients with toxic neutrophils did not alter metabolism of control neutrophils. The mechanism responsible for increased metabolic activity and histochemical NBT reduction in toxic neutrophils is unknown.