Clinical studies in critically ill patients suggest an increased rate of septicemia during stress ulcer prophylaxis with H2-blockers when compared with sucralfate, a topically active compound. In the present study we examined the effect of stress ulcer prophylaxis with sucralfate as compared with ranitidine versus untreated animals in a rat model on intestinal flora and on the translocation of bacteria from the intestinal tract. The translocation of bacteria was also determined after induction of hemorrhagic shock and, in addition, we examined bacterial translocation in animals infected with a multiple resistant Escherichia coli and following antibiotic therapy with vancomycin and gentamicin during stress ulcer prophylaxis with and without hemorrhagic shock. Male Wistar rats, which received standard meals either without stress ulcer prophylaxis or with ranitidine/sucralfate were investigated. After induction of hemorrhagic shock we analysed qualitatively and quantitatively the bacterial flora in the gastrointestinal tract, blood, mesenteric lymph nodes and visceral organs (liver, spleen). In the absence of shock no changes of the intestinal flora and no translocation of bacteria from the gut were observed in control animals nor during stress ulcer prophylaxis. However, after induction of hemorrhagic shock there was a pronounced bacterial translocation in control animals and during ranitidine, whereas the translocation rate was reduced in animals treated with sucralfate (p < 0.05). During massive E. coli challenge both without and with shock a significantly higher rate of translocation was found in all three experimental groups there were no significant differences between the three groups. We conclude that a) bacterial translocation is low or absent in healthy animals, b) hemorrhagic shock induces a massive increase in bacterial translocation, c) stress ulcer prophylaxis with sucralfate reduces translocation of bacteria during the shock state and c) during massive bacterial overgrowth and/or concomitant shock none of the treatments can reduce the massively elevated rate of bacterial translocation.