The intravenous administration of hydrogen peroxide has been reported to benefit patients with pneumonia and to reduce Plasmodium parasitemia in experimentally infected mice. We assessed the antibacterial activity of intravenously infused hydrogen peroxide against hydrogen peroxide-susceptible Escherichia coli (MBC of hydrogen peroxide, 0.23 mM) in experimentally infected rabbits. No decrease in the level of bacteremia was detected at the maximum intravenous infusion rate of hydrogen peroxide physiologically tolerated by the rabbits (2.0 mumol/h). Moreover, the addition ex vivo of greater amounts of hydrogen peroxide to human or murine blood containing E. coli resulted in no detectable antibacterial action. In contrast, ethyl hydrogen peroxide, which is not affected by catalase, was bactericidal when added ex vivo to human blood containing E. coli. These results suggest that extracellular hydrogen peroxide, whether of exogenous or endogenous origin, does not have antibacterial activity in the blood of animals having even low levels of catalase.