Decontamination of the digestive tract with antimicrobial agents has been used for prevention and therapy of bacterial translocation. With regard to the well-described endotoxin-releasing properties of these agents, the question arises as to whether their enteral administration might result in an increased amount of intestinal endotoxins entering the circulation. Immunocompromised Wistar rats were intraduodenally challenged with live E. coli. Control animals received saline solution, decontaminated rats were treated with either tobramycin plus polymyxin B or ciprofloxacin alone through the duodenal tube. Plasma endotoxin activity and blood bacteria count were measured hourly over an observation period of 5 h. The intestinal bacterial count was determined at the end of the experiment. Gut decontamination in both groups receiving antimicrobial agents resulted in elevated plasma endotoxin levels compared with nondecontaminated controls. Maximum endotoxin levels were found to be 5-6 times higher in the ciprofloxacin group than in the control group and 2 times higher than in the tobramycin/polymyxin group. No positive blood cultures were detected. Intestinal bacterial count was similar in both treatment groups. Enterally applied antimicrobial agents bear an elevated risk of endotoxemia during the initial phase of gut decontamination. The amount of endotoxin translocating from the digestive tract to the circulation varies with the agents used. Polymyxin only partially reduced the observed endotoxin leakage from the gut.