Vancomycin penetration into the fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiberoptic bronchoscopy with bronchoalveolar lavage on 14 critically ill, ventilated patients who had received the drug for at least 5 days. The apparent volume of epithelial lining fluid (ELF) recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. Vancomycin levels in ELF ranged from 0.4 to 8.1 ,ug/ml (mean, 4.5 ,iglml), while the mean simultaneous level of the drug in plasma was 24 ,ug/ml (range, 9 to 37.4 ,ug/ml). There was a significant relationship (r = 0.64, P < 0.02) between vancomycin levels in plasma and those in ELF, with a correlation whose slope (0.15) indicated that the blood-to-ELF ratio of drug penetration was 6:1. Using the albumin concentration in ELF as a marker of lung inflammation, we found that vancomycin penetration was higher in patients with ELF albumin values of >3.4 mg/ml than in patients with normal values (<3.4 mg/ml) (P < 0.02). These results suggest that the vancomycin distribution includes the ELF of the lower respiratory tract at a concentration that is dependent upon the levels in blood and the alveolar capillary membrane protein permeability. These concentrations were well above the MICs for most staphylococci and enterococci.Vancomycin, a glycopeptide antibiotic, is used worldwide to treat deep-seated gram-positive bacterial infections caused by staphylococci or enterococci resistant to 1-lactams or patients with significant allergy to ,B-lactams (18, 29). These pathogens may be responsible for nosocomial pneumonia, which is a common and life-threatening problem complicating the management of patients receiving mechanical ventilation (24). Successful treatment of bacterial pneumonia will, however, depend upon adequate delivery of the antibiotic to the area of infection. Unfortunately, little is known about the penetration of vancomycin into lung tissue.With the advent of the technique of bronchoalveolar lavage (BAL), it is now possible to directly obtain a sample of the fluid and cells lining the epithelial surface of the human lower respiratory tract (4, 21). Therefore, in an attempt to quantify the penetration of vancomycin into lung alveoli, we obtained both BAL fluid and blood samples from critically ill patients who were receiving this antibiotic as part of their therapy. In addition, we investigated whether vancomycin penetration was modified by the inflammatory status of the lung.( chanically ventilated and, because of the presence of a new pulmonary infiltrate with fever and/or purulent tracheal secretions, underwent flexible fiberoptic bronchoscopy with a protected specimen brush (PSB) and BAL a few days later, after the initiation of treatment with vancomycin. For each patient, the following clinical variables were recorded: age, sex, weight, disease severity score on admission (as assessed by the APACHE II score) (13), creatinine clearance, and lung injury score as previously described by Murray et al. (17). E...