Primary host defense against infecting microbes is provided by the humoralphagoxyte axis of immunity. The antigen-specific immunoglobulins and components of the classical and alternative complement pathways that comprise the humoral aspect of the axis provide the information that directs the phagocyte effectors of microbial action. Humoral immunity as well as phagocyte function have been reported to be defective in burn patients. Upon stimulation, phagocytes undergo gross alterations in metabolism characterized by increased carbohydrate metabolism via the dehydrogenase of the hexose monophosphate shunt and increased nonmitochondial O2 consumption. Both activities reflect the expenditure of energy for reduction of O2 and the generation of potent microbicidal oxygenating agents. Chemiluminigenic probing allows ultrasensitive measurement of stimulated phagocyte oxygenation activity. A chemiluminigenic probe CLP is defined as a substrate susceptible to oxygenation yielding electronically excited products that relax by photon emission, chemiluminescence CL. As such, the generation of oxygenating agents by activated phagocytes can be measured as CLP-dependent CL by single photon counting. This article provides a description of the recently developed CLP approach for direct measurement of phagocyte oxygenation activity using microliter quantities or unseparated whole blood, and the application of this method to evaluating phagocyte function in the burn patient.