Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal tract to extraintestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. The major mechanisms promoting bacterial translocation in animal models are: (a) disruption of the ecologic equilibrium to allow intestinal bacterial overgrowth, (b) deficiencies in host immune defenses, and (c) increased permeability of the intestinal mucosal barrier. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis. Studies are presented of attempts to delineate the mechanisms promoting bacterial translocation utilizing animal models of intestinal bacterial overgrowth, immunosuppression, T-cell deficiencies, solid tumors, leukemia, diabetes, endotoxemia, hemorrhagic shock, thermal injury, bowel obstruction, bile duct ligation, protein malnutrition and parenteral nutrition. Also described are the use of selective antibiotic decontamination or nonspecific macrophage immunomodulators in attempts to reduce bacterial translocation from the gastrointestinal tract.