The persistent presence of polymorphonuclear neutrophils (PMN) in airways is the hallmark of cystic fibrosis (CF) disease. The aim of this study was to assess the PMN adherence, the percentage of apoptotic airway PMN and production of cytokines IL-6 and IL-8 when airway PMN are in contact with airway epithelial cells. Before the co-culture, freshly isolated CF airway PMN have greater spontaneous and TNF--induced apoptosis compared to blood PMN from the same CF patients, and from airway PMN of non-CF patients. We then examined co-cultures of PMN isolated from airways of CF and non-CF patients with bronchial epithelial cells bearing mutated cftr compared to cftr-corrected bronchial epithelial cells. After a 18h co-culture, the number of CF airway PMN adhered on cftr-deficient bronchial epithelial cells was 2.3-fold higher compared to the co-culture of non-CF airway PMN adhered on cftr-corrected bronchial epithelial cells. The percentage of CF apoptotic airway PMN (9.5 ± 0.2%) adhered on cftr-deficient bronchial epithelial cells was similar to the percentage of non-CF apoptotic airway PMN adhered on cftr-corrected bronchial epithelial cells (10.3 ± 0.7%). The levels of IL-6 and IL-8 were enhanced by 6.5- and 2.9-fold, respectively, in the co-culture of CF airway PMN adhered on cftr-deficient bronchial epithelial cells compared to the co-culture of non-CF airway PMN adhered on cftr-corrected bronchial epithelial cells. Moreover, blocking surface adhesion molecules ICAM-1, VCAM-1 and E-selectin on cftr-deficient bronchial epithelial cells with specific monoclonal antibodies inhibited the adherence of CF airway PMN by 64 %, 51 % and 50 %, respectively. Taken together, our data suggest that in patients with CF, an high number of non-apoptotic PMN adhered on airway epithelium associated with elevated levels of IL-6 and IL-8 may contribute to sustained and exaggerated inflammatory response in CF airways.