The bactericidal/permeability increasing protein is a major element in the host defense against Gram-negative bacteria and endotoxin, acting intracellularly in the polymorphonuclear leukocyte. As an isolated protein, bactericidal/permeability increasing protein also acts as an extracellular bactericidal and endotoxin-neutralizing agent and, when injected, protects animals against lethal effects of Gram-negative bacteria and endotoxin.