INTRODUCTION: Surfactant protein (SP)-B is a hydrophobic protein secreted within pulmonary surfactant that facilitates the adsorption of surface-active lipids to the air-liquid interface of the alveoli and increases alveolar stability. SP-B may also have anti-inflammatory properties. It is implicated in decreasing the pulmonary inflammatory response to bacterial lipopolysaccharide. However, the expression and function of SP-B in the sinonasal cavities has not been elucidated. Our objective was to detect the presence of SP-B, measure alterations in several forms of chronic rhinosinusitis (CRS), and localize cellular protein expression. MATERIALS/METHODS: Sinus mucosal biopsies were performed in patients with allergic fungal rhinosinusitis (AFRS), nonatopic CRS with nasal polyposis (NP), and cystic fibrosis (CF) and in healthy controls. SP-B mRNA was measured in CRS and control patients using quantitative polymerase chain reaction. Immunoblot analysis and immunolocalization of SP-B were also performed. RESULTS: CF (n = 4) showed significantly increased levels of SP-B (169-fold) mRNA (P = .004) when compared with controls (n = 5). CRS with NP (n = 5) and AFRS (n = 7) also demonstrated elevated levels of SP- B (14-fold and 4-fold, respectively) when compared with the control group, although these were not statistically significant. Immunoblot analysis confirmed the presence of the translated product, and immunolocalization revealed expression in the epithelium and submucosal glandular elements. CONCLUSION: This is the first study to detect and characterize SP-B in human sinus mucosa. Furthermore, SP-B is significantly up-regulated in CF CRS. © The American Laryngological, Rhinological & Otological Society, Inc.