The objective of the present work was to assess the possible mechanisms of the poor efficiency of selective decontamination of the digestive tract (SDD) in medical and surgical intensive care unit (ICU) patients. Sixty-four consecutive mechanically ventilated patients received gut decontamination with polymixin E, gentamicin and amphotericin B via a nasogastric tube and were assessed for oropharyngeal, gastric and fecal colonization and for the presence of each antibiotic in the stomach and feces. A decrease in fecal colonization withEscherichia coli was observed over 20 days but not with other gram-negative bacteria or gram-positive cocci. Fifteen and 26 % of the fecal colonizing gram-negative bacteria were resistant to polymixin E and gentamicin, respectively, at admission. These proportions increased to up to 50 % after 16 days of treatment. Although 50 % of staphylococci were initially sensitive to gentamicin, all strains were resistant to this drug after four days of SDD. Both antibiotics were found in concentrations of less than 20 µg/g in 11 of 38 stools. Of these 38 stools, nine were not contaminated, 20 were colonized with resistant bacteria and 16 with strains sensitive to one antibiotic present in the stool. Therefore, the poor efficiency of gut decontamination observed was probably due to the great proportion of resistant strains on admission of the patients, to the selection of such resistant strains with SDD, to poor intestinal transit of the antibiotics, and to inactivation of the drugs by the feces. These results support stringent monitoring of fecal colonization in patients undergoing SDD in order to detect the fecal carriage of gram-positive and multiresistant gram-negative bacteria.