Background: Surfactant-associated proteins (SP) A and D are in the family of collectin proteins that play an integral part in the innate defense system. SP-A and SP-D expression and function are altered in a variety of inflammatory and infectious diseases of the lungs, such as asthma, allergies, and cystic fibrosis. Our prior studies are the first to identify the presence of these proteins in the human sinonasal cavity. The objective of this study was to immunolocalize SP-A and SP-D in human sinonasal tissue. Methods: Sinonasal mucosal biopsies were performed in patients with various forms of chronic hyperplastic rhinosinusitis with nasal polyposis and nondiseased mucosa from patients undergoing transsphenoidal hypophysectomy. (n 10) Immunolocalization of surfactant proteins was performed with antibodies to SP-A and SP-D using immunoperoxidase staining technique. Isotype-negative controls were performed on all specimens. Results: Analyses of mucosal biopsy specimens from human sinonasal tissue reveals staining within respiratory and intermediate (metaplastic)-type surface epithelium. In addition, staining was intense in the submucosal ductal epithelium of the seromucinous glands. These properties appear to be consistent regardless of disease state and location within the sinuses. Conclusion: This is the first study to immunolocalize SP-A and SP-D in sinonasal human mucos. These are secreted proteins that are intricately involved in innate immunity in the lungs. Their secretion in the upper airway indicates that future studies may allow manipulation of these proteins and development of novel treatments for sinonasal pathology. Copyright © 2006, OceanSide Publications, Inc., U.S.A.