Vancomycin penetration in epithelium lining fluid was studied in ten mechanically ventilated patients with methicillin-resistant Staphylococcus aureus pneumonia 24 hours after the onset of treatment. Vancomycin was given intravenously at a daily dose of 30 mg/kg. Vancomycin levels were detectable in four patients (range, 1-2.77 micrograms/ml). Concordance between high plasma concentrations (> 20 micrograms/ml) and detectable vancomycin levels in epithelium lining fluid was noted. These results suggest that the pulmonary disposition of vancomycin remains low for most patients 24 h after the onset of treatment compared with the minimum inhibitory concentrations for most gram-positive organisms. One therapeutic goal of vancomycin treatment could be to obtain through plasma levels of 20 micrograms/ml. Further studies are required to determine the clinical relevance of these observations.