Serial maxillary sinus aminoglycoside lavage is an adjunctive technique increasingly employed in a variety of areas in cystic fibrosis (CF). It may be helpful in reducing revision rates for sinus surgery, in lowering rates of bronchial pseudomonal colonization after lung transplantation and in the evolving field of gene therapy for CF. The goal of this study was to assess the utility of the maxillary sinus as a model for gene transfer in cystic fibrosis. We performed serial maxillary sinus lavage, in accordance with published protocols, using tobramycin in a randomized series of five CF subjects. Lavage was performed for up to 10 days and sequential magnetic resonance imaging (MRI) scans were taken at zero, 10, 30, 60, 120 and 180 days. The 30 MRI scans were blindly scored by two examiners on the parameters of maxillary sinus aeration, averaged over the five time intervals, was significantly improved (p<0.05) in the lavaged sinus. This study provides the first systematic image-based measure of efficacy of maxillary sinus aminoglycoside lavage, a major element of a number of clinical protocols used in the treatment of CF. The prolonged increase in aeration after lavage suggests that any further improvement potentially achievable after gene transfer would be difficult to detect, limiting the value of this system as a model of clinical efficacy of gene transfer in CF.