The purpose of this study was to explore the causative effects of high-velocity bullet injury (5.56 mm, 930 m/sec) combined with hemorrhagic shock on gut-derived endotoxemia and multiple system organ dysfunction or failure. The concentration of endotoxin in both portal and systemic blood was markedly increased after gunshot wounds together with hemorrhagic shock (p < 0.05-0.01). The portal/systemic lipopolysaccharide ratio persistently decreased in the combined wound (CW) group at 24 to 72 hours after injury, and it was much lower in the CW group than that in the single gunshot wound (SW) group. Also, a significant increase of fecal endotoxin content was found in the CW group as compared to the SW group (118.30 +/- 75.36 vs. 8.89 +/- 3.32 micrograms/g, p < 0.01), which was paralleled with the population of gram-negative bacilli in the intestinal tract. The incidence of multiple system organ failure, multiorgan dysfunction (including single organ failure) in the CW group were 30.8% (4 of 13) and 38.5% (5 of 13), respectively. These results suggested that severe trauma could lead to gut origin endotoxemia and bacterial translocation, which might play an important role in the pathogenesis of sepsis and multiple system organ failure following gunshot wounds.