Critically ill patients admitted to the surgical intensive care unit since 1982 have been treated prophylactically with oral non-absorbable antibiotics combined with parenteral cefotaxime. A mixture of polymyxin E, tobramycin and amphotericin B has been administered via a nasogastric tube and also applied topically to the buccal mucosa. This regimen has proven to be highly effective in reducing the infection rate. The present study evaluated the occurrence of resistant bacteria with this regimen during a 30-month period, in 164 patients with multiple trauma. No increase in the percentage of patients with acquired drug-resistant Gram-negative bacilli was found during this period. Colonization of the oral cavity and/or gastro-intestinal canal by polymyxin E-resistant strains (invariably Proteus spp.) occurred in 8% of patients, and by tobramycin-resistant bacilli (Escherichia coli or Acinetobacter or Pseudomonas spp.) in 4%. Intestinal colonization with cefotaxime-resistant strains (e.g. Pseudomonas, Acinetobacter or Enterobacter spp.) was observed in 17 patients (10%). Of these strains 82% were eliminated within one week by the oral non-absorbable antibiotics. Colonization of the respiratory tract, urinary tract or wounds with cefotaxime-resistant Gram-negative bacilli occurred in only three patients (2%).