Susceptibility to infection in compromised hosts is a clinically important problem. The role of granulocytes in the defense against infection is apparent from the severe infections that occur in patients with granulocytopenia or a defective neutrophil function. When phagocytes interact with soluble or particulate stimuli, the cells generate reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide, which can be measured using a luminol-dependent chemiluminescence (CL) method. The CL response of whole blood reflects the ability of the granulocytes to generate ROS upon stimulation, and the opsonic activity of serum when zymosan particles or bacteria without opsonization are used as stimuli. To clarify the primary systemic host defense against invading bacteria in various compromised hosts, we applied this method to evaluate the production of ROS in the granulocytes of a patient. The values of zymosan- or bacteria induced whole blood CL were lower in patients with diseases such as liver cirrhosis, SLE, AIDS and burns in comparison with that in healthy adults. Furthermore, the whole blood CL in the blood of these patients was less augmented upon stimulation with zymosan at the onset of sepsis or pneumonia. To clarify why the whole blood CL exhibits lower response in the acute phase of bacterial infections, we investigated the priming effects of lipopolysaccharide (LPS) or TNF-α on the CL response. These effects were significantly decreased in the blood of these patients when compared with that of healthy persons. This lower response to LPS or TNF-α supports our finding that a patient's phagocytes cannot be fully activated when bacterial infections occur.