In patients with clinical suspicion of pneumonia, quantitative cultures of protected brushing specimens (PBS) yielding greater-than-or-equal-to 10(3) CFU/ml of at least one microorganism have been found useful for differentiating airway colonization and lung infection, especially in mechanically ventilated patients. The amount of secretions collected by protected catheter brushing is small and difficult to determine accurately. Thus, the clinical significance of PBS cultures yielding organisms in concentrations greater-than-or-equal-to 10(2) but < 10(3) CFU/ml, in the absence of active antimicrobial treatment, is unknown. The 34 consecutive results of PBS cultures yielding organisms in concentrations greater-than-or-equal-to 10(2) but < 10(3) CFU/ml in 30 patients under mechanical ventilation or weaned for less-than-or-equal-to 4 days were prospectively studied. No patients were receiving agents active on the organism recovered. In 5 cases, the diagnosis of pneumonia was ruled out by recovery without treatment (n = 4) or negative postmortem lung cultures (n = 1). A second PBS was cultured in 29 episodes (2.7 +/- 1.8 days after the first PBS). In 12 instances (Group 1), cultures of the second PBS yielded greater-than-or-equal-to 10(3) CFU/ml of the same organism as that found in the first PBS (S. pneumoniae, 1; S. aureus, 1; H. influenzae, 1; E. coli, 1; P. aeruginosa, 4; and A. baumannii, 4), and these patients were therefore treated with appropriate antibiotics. A total of 17 patients had a negative repeat PBS culture (no growth or trivial concentrations) and were considered free of pneumonia and given no antibiotic treatment for this episode. In the 22 episodes (Group 2) in which pneumonia was ruled out through recovery without treatment, or a negative second PBS culture, or a negative lung specimen culture, the organisms recovered from the initial PBS were as follows: S. aureus, 7; E. cloacae, 1; P. aeruginosa, 9; X. maltophilia, 2; A. baumannii, 2; and C. albicans, 1. Comparison of Group 1 and Group 2 revealed no differences for age (60.4 +/- 15.8 versus 58.9 +/- 18.7 yr) or simplified acute physiology score (11.2 +/- 4.4 versus 11.8 +/- 4.4). In contrast (after exclusion from the analysis of the 4 patients who had two episodes), Group 1 patients had a higher fatality rate (6 of 8 versus 4 of 18, p < 0.04). Treating all patients with a PBS culture yielding organisms in concentrations greater-than-or-equal-to 10(2) but < 10(3) CFU/ml would lead to overtreatment in most cases. Nevertheless, because its result is unpredictable a second PBS must be obtained in patients with persistent clinical suspicion of pneumonia, to identify those patients who require treatment.