To obtain accurate information on distal bronchial microflora during acute exacerbation in patients with chronic bronchitis, we prospectively studied 54 such patients who had been receiving mechanical ventilation because of hypercapnic respiratory failure. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient within the first 24 h after admission. Cultures of protected brush specimens demonstrated no growth in 27 patients (50%). With the exception of fever (38.2 +/- 0.8 versus 37.7 +/- 0.6 degrees C; p less than 0.05), the initial severity of the episode of exacerbation was similar in patients with and without infection. A total of 44 organisms were isolated in the 27 patients with positive cultures; the predominant pathogens were Hemophilus spp. and Streptococcus spp. (involved in 74% of cases), but other organisms were isolated in 12 of 27 patients. Mortality rates, duration of mechanical ventilation, and duration of hospitalization were not significantly different between patients with bronchial microflora treated with appropriate antimicrobial therapy (n = 27) and patients without bronchial microflora either receiving empirical antibiotic therapy (n = 18) or not (n = 9). These data suggest that distal bronchial infection due to the usual pathogens, as far as shown by protected specimen brush cultures, may not be the sole or even the predominant cause of acute exacerbation of chronic bronchitis in patients requiring mechanical ventilation.