The high incidence of serious opportunistic infection following human burn injury has been well documented. Investigations of the mechanisms of this acquired susceptibility have demonstrated several defects in phagocytic defenses. An established rat burn infection model was modified for study of neutrophil function in animals with a 60% burn injury. These 350-g rats received a 35-ml saline resuscitation, and when not further stressed, 80% of the animals survived to healing. Burned animals were found to have decreased inflammatory responses to intraperitoneal injections of heat-killed Pseudomonas aeruginosa, Staphylococcus aureus, and sterile sodium caseinate. These reductions could not be explained by neutropenia. Prior immunization with heat-killed Pseudomonas did not improve the inflammatory response to homologous organisms injected intraperitoneally, but levamisole treatment did improve the imflammatory response. Epinephrine injection (intravenous) showed that burned animals have a markedly reduced proportion of marginated neutrophils but an increase in total peripheral neutrophil counts. The stress hormones corticosterone and catecholamines were elevated during times of decreased inflammatory responsiveness; additionally, neutrophils from burned animals had decreased adherence to nylon fiber. Serum from burned animals decreased in vitro adherence and chemotaxis of purified normal rat neutrophils.