The efficacy of selective decontamination of the oral cavity and GI-tract in the treatment of established gram-negative pneumonia in critically ill patients was evaluated in a prospective open trial. 25 patients with pneumonia caused by Enterobacteriaceae or Pseudomonadaceae were studied. All patients were mechanically ventilated (range 2-60 days). Non-absorbable antibiotics (polymyxin E 100 mg, tobramycin 80 mg, amphotericin B 500 mg) were administered through the nasogastric tube four times a day. The oral cavity was decontaminated with an ointment containing 2% of the same antibiotics, applied to the buccal mucosa four times a day. For systemic therapy a combination of tobramycin (3-6 mg X kg-1) with either cefotaxim (50-100 mg X kg-1) or ceftazidime (100 mg X kg-1) was given both intravenously and by aerosol (50% IV dose/5 ml saline) four times a day. Eradication of pathogens from the respiratory tract was achieved in 24 patients within 9 days (median 5 days). The cure rate was 96%. Two patients had a relapse. Neither recolonization with resistant organisms nor supra-infections were found for the remaining period of mechanical ventilation (up to 60 days), also after systemic/aerosol therapy had been discontinued. Only 3 patients died (12%).