OBJECTIVES: Test the hypothesis that the link between respiratory viruses and pulmonary exacerbation in cystic fibrosis (CF) reflects increased frequency or severity of lower airways infection. STUDY DESIGN: Molecular respiratory viral panels (RVPs), cell counts, and quantitative bacterial cultures were assessed in 235 bronchoalveolar lavage fluid (BALF) samples from 138 children with CF. Relationships among the data were analyzed using multivariate methods. RESULTS: RVPs were positive in 67 (28.5%) BALF samples from 52 (37.7%) patients, with rhinovirus/enterovirus most common (82.4% of RVP+). RVP+ patients were younger (5.4 years, IQR 3.0-9.7 vs. 8.0 years, IQR 3.5-12.9; P < 0.01), more likely to have respiratory symptoms (74.6% vs. 55.2%, P < 0.01), and had higher BALF percent neutrophils (70.5%, IQR 46-85% vs. 59.3%, IQR 34-77%; P < 0.05). Percent predicted FEV1 at bronchoscopy was diminished from baseline in both groups, but recovered in the RVP- (90.2 +/- 22.2% vs. 89.6 +/- 19.7%, P = 0.62) but not the RVP+ subjects (95.7 +/- 21.1% vs. 89.1 +/- 18.0%, P < 0.05). RVP status did not alter recovery rates of typical CF respiratory pathogens including Staphylococcus aureus (44.8% vs. 42.9%) and Pseudomonas aeruginosa (25.4% vs. 25.6%). However, common respiratory pathogens (Haemophilus species, Moraxella species, and Streptococcus pneumoniae) were recovered more frequently from RVP+ samples independent of age (OR 3.6, 95% CI 1.8-7.5, P < 0.001). CONCLUSIONS: Respiratory viruses were frequently detected in BALF from CF patients and associated with markers of disease severity. Respiratory viruses did not impact frequency or severity of infection with typical CF pathogens, but rates of infection with common respiratory pathogens were increased. This finding may have treatment implications.