Granulocytes' in vitro bactericidal capacity for certain bacteria depends on an adequate environmental oxygen supply. Oxygen available to granulocytes in infected tissue is decreased by local conditions and can be altered significantly by small changes in its inspired concentration. We modified Burke's and Miles' bacteria-injection model in animals to test the effect of breathing 12%, 21%, and 45% oxygen on the size of lesions produced by intradermal injections of Escherichia coli. Moderately increased inspired oxygen concentrations (fraction of inspired oxygen [Flo2]) significantly decreased the size and number of necrotic lesions, whereas hypoxia increased both. Increasing Flo2 to 45% after three and 24 hours of hypoxia also significantly decreased lesion size. Suppression of infection by moderate hyperoxia is comparable with that reported by Burke after timely, adequate doses of type-specific antibiotics.