As a consequence of diminished nitric oxide synthase (NOS) protein concentration, the airway concentration of nitric oxide (NO) is reduced in patients with cystic fibrosis (CF). This appears to lead to a reduced elimination of such microorganisms as Pseudomonas aeruginosa. The objective of this study was to analyze whether inducible (iNOS), endothelial (eNOS) and neuronal (bNOS) NOS are reduced at mRNA level and if so whether this is caused directly by the defective CF transmembrane conductance regulator (CFTR). Nasal polyps from three patients with CF and four otherwise healthy patients were obtained. The expression of the three NOS isoenzymes was quantified using real-time PCR. The iNOS expression was assessed in colon carcinoma cells (CaCo) transfected with a normal and a mutated (DeltaF508) CFTR. In CF patients, iNOS mRNA expression was 10-to 20-fold and bNOS gene expression was one-fifth to one-tenth that in control patients (P < 0.001). In CaCo cells, iNOS gene expression under basal and endotoxin-stimulated conditions did not differ between cells transfected with a mutated CFTR and those transfected with an intact CFTR. This observation suggests that cystic fibrosis is associated with reduced iNOS and bNOS gene expression in nasopharyngeal tissue, possibly disturbing the barrier against infective agents already at the site of entrance.