Identifying lower respiratory pathogens in young, non expectorating cystic fibrosis (CF) patients has been problematic. Bronchial secretions are difficult to obtain, and little is known about lower airway flora in these patients. We collected simultaneous bronchial and oropharyngeal specimens in 43 CF patients in optimal respiratory status, including both expectorating (17) and nonexpectorating (26) patients, to determine the predictive value of oropharyngeal cultures for identifying lower airway pathogens. An additional goal was to characterize the lower respiratory flora of these patients. Predictive values were defined as the proportion of oropharyngeal culture results that accurately reflected the results of bronchial cultures. Predictive values of positive oropharyngeal cultures in nonexpectorating patients were 83% (95% confidence interval 36 to 100%) for Pseudomonas aeruginosa and 91% (59 to 100%) for Staphylococcus aureus. Predictive values of negative oropharyngeal cultures were lower: 70% (48 to 86%) for R aeruginosa and 80% (52 to 96%) for S. aureus. A relatively high proportion of nonexpectorating CF patients less than 10 yr old had R aerusginosa (11 of 24, 46%) or Klebsiella species (5 of 24, 21%) in their lower airways. The isolation of Klebsiella was associated with younger age (p = 0.03) and recent administration of antistaphylococcal antibiotics (p = 0.05). Our results suggest that oropharyngeal cultures yielding R aeruginosa or S. aureus are highly predictive, but such cultures lacking these organisms do not rule out the presence of these pathogens in the lower airways of CF patients.