The incidence of respiratory tract infections was determined in 59 multiple trauma patients requiring prolonged intensive care (greater than 5 days) and receiving no antibiotic prophylaxis. Early pneumonia (less than 48 hr) with S. aureus, S. pneumoniae, and/or H. influenzae was found in 44% of patients. Secondary colonization of the oropharynx and respiratory tract with ICU-associated Gram-negative bacilli followed by pneumonia occurred in 12 patients (20%). The overall incidence of respiratory tract infections was 59%. In a prospective open trial three prophylactic antibiotic regimens were compared: 17 patients were treated with intestinal decontamination using nonabsorbable antibiotics (polymyxin E 400 mg, tobramycin 320 mg, amphotericin B 2,000 mg/day). No difference in infection rate was found. Twenty-five patients were treated with intestinal and oropharyngeal decontamination using an ointment containing 2% of the same antibiotics. Secondary colonization and infection of the respiratory tract with Gram-negative bacilli was significantly reduced (p less than 0.001). The incidence of early (Gram-positive) infections, however, was unchanged. Another group of 63 patients was treated with systemic antibiotic prophylaxis during the first days in combination with oropharyngeal and intestinal decontamination. The incidence of early pneumonia was significantly reduced (p less than 0.001). Five patients (8%) developed an infection. Superinfections were not observed.