Background: Transgenic cystic fibrosis (CF) murine models do not develop spontaneous lung or sinus disease, 2 major causes of morbidity in human CF patients. Because of these limitations, transgenic cystic fibrosis transmembrane conductance regulator (CFTR)-/- pigs have been developed and are currently being characterized. These CF animal models have phenotypes closely resembling that of human CF subjects. The objectives of the current study were to develop primary porcine nasal epithelial (PNE) cultures and evaluate their usefulness as a means to investigate sinonasal transepithelial transport and CFTR function. Methods: PNE derived from the septum or turbinates of CFTR+/+ and CFTR-/- pigs were cultured at an air-liquid interface to confluence and full differentiation. Epithelial monolayers were mounted in Ussing chambers to investigate pharmacologic manipulation of ion transport. Ciliary beat frequency (CBF) and scanning electron microscopy of monolayers were used to indicate degree of ciliation and cell differentiation. Results: Stimulation of CFTR-mediated anion transport (ΔIsc in μA/cm2) was significantly greater in epithelia derived from the septum when compared to turbinates (33.04 ± 1.17 vs 18.9 ± 0.73; p < 0.05). Cyclic adenosine monophosphate (cAMP)-activated Cl- secretion was absent in CFTR-/- and present in CFTR+/+ epithelia. Calcium-activated Cl- (CaCC) secretion was increased in CF; however, overall Cl- transport through CaCCs was very low. Degree of ciliation (90%) and CBF were similar between groups. Conclusion: Septal PNE exhibit a robust ion transport phenotype and indicate CFTR-/- sinus disease could be attributable to diminished alternative pathways for Cl- transport. Overall, PNE have similarities to human respiratory epithelia not demonstrated in murine cells and represent useful in vitro models for studying CF sinus disease. © 2014 ARS-AAOA, LLC.