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Various disease states are associated with eosinophilia and the release of eosinophil peroxidase (EPO) into the microenvironment. The present study targets the effects of low levels of EPO on macrophage (MØ) phagocytosis and intracellular killing of Candida albicans as well as MØ oxidative activity measured as the luminescence product of luminol dioxygenation. Resident murine peritoneal MØ were exposed to various concentrations of EPO. Chemiluminescence data indicate that nanomolar concentrations of EPO markedly enhanced the dioxygenation activity (respiratory burst) of MØ. In other studies, the exposure of MØ to 0.17 μM EPO for 10 min. enhanced MØ-mediated candidacidal activity 10 fold. The above data indicate that EPO enhances certain MØ functions. Also the results illustrate a previously un-recognized interaction between eosinophils and MØ and implicate yet another possible role for EPO in host defenses against disease.