The virulence of Bacillus anthracis has been attributed to a tripartite toxin composed of three proteins designated protective antigen, lethal factor, and edema factor. The effects of the toxin components on phagocytosis and chemiluminescence of human polymorphonuclear neutrophils were studied in vitro. Initially, it was determined that the avirulent Sterne strain of B. anthracis (radiation killed) required opsonization with either serum complement or antibodies against the Sterne cell wall to be phagocytized. Phagocytosis of the opsonized Sterne cells was not affected by the individual anthrax toxin components. However, a combination of protective antigen and edema factor inhibited Sterne cell phagocytosis and blocked both particulate and phorbol myristate acetate-induced polymorphonuclear neutrophil chemiluminescence. These polymorphonuclear neutrophil effects were reversible upon removal of the toxin components. The protective antigen-edema factor combination also increased intracellular cyclic AMP levels. These studies suggest that two of the protein components of anthrax toxin, edema factor and protective antigen, increase host susceptibility to infection by suppressing polymorphonuclear neutrophil function and impairing host resistance.