OBJECTIVE To determine a selected concentration of sodium hypochlorite (NaOCl) in saline solution for nasal lavage and evaluate its clinical efficiency in the treatment of symptomatic patients with persistent, Staphylococcus aureus (SA) associated rhinosinusitis (RS). MATERIAL AND METHODS In vitro tests for cilia and epithelial cell viability were done on reconstituted primary epithelial cells in vitro. Cells were exposed for 5 and 15 minutes twice daily for 5 consecutive days to one of the following conditions, (1) saline, (2) 0.5% NaOCl in saline, and (3) 0.05% NaOCl in saline. In order to evaluate tolerance, immunostaining was done for ezrin and F-actin network and observed with confocal microscopy. The patients (n=20) were all persistent SA symptomatic carriers, with unique patient-specific SA clonotypes, and multiple infection recurrence despite effective systemic antibiotic therapy. Each patient applied first saline alone for 3 months followed by saline + 0.05% NaOCl solution, as nasal lavage twice daily on both nostrils for 3 months. Symptom intensity and endoscopic findings were recorded with visual analogue scale (VAS). Nasal airway resistance (NAR) and nasal Nitric Oxide (NO) levels were measured before and after the saline lavage regimen, and after the saline + NaOCl treatment. RESULTS F-actin network loss and decreased expression of ezrin were significant in cells exposed to 0.5%, but not in those exposed to 0.05% NaOCl. These changes were more obvious when exposed for 15 min. than 5 min. daily. The nasal lavage with 0.05% NaOCl in saline was well tolerated and a significant improvement in nasal obstruction (p = 0.001), posterior nasal discharge (p = 0.018), olfaction (p = 0.007) and headache (p = 0.009) was demonstrated. Significant improvement was also recorded in nasal endoscopic grading of oedema (p = 0.001), erythema (p = 0.001), purulent discharge (p = 0.002), nasal crusts (p = 0.001), and NAR (p = 0.05) as measured by rhinomanometry. There was no significant improvement in nasal NO production or subjective anterior nasal discharge. Bacteriological cultures of middle meatus secretions collected one month after the end of the treatment revealed the persistence of SA. CONCLUSION Nasal lavage with 0.05% NaOCl solution in saline is suitable for long-term use and seems to be a good alternative to lavage with saline alone in the management of symptomatic RS associated with recurrent SA infections due to patient-specific SA clonotypes.