The combination of bacteria and blood in a wound can have lethal consequences, probably because hemoglobin iron supports prolific bacterial growth. Rats inoculated intraperitoneally with pathogenic Escherichia coli and small amounts of hemoglobin die. Simultaneous administration of haptoglobin, a naturally occurring hemoglobin-binding protein, fully protects against lethality. Therefore, haptoglobin may not only accelerate the clearance of free hemoglobin, but also limit its utilization by adventitious bacteria. Haptoglobin may have therapeutic potential in the treatment of life-threatening, hemoglobin-driven bacterial infections.