CFTR (cystic fibrosis transmembrane conductance regulator) is a cAMP-activated chloride channel that regulates electrolyte and water transport. The present study investigated the expression and localization of CFTR in human gingiva and explored the possible association of CFTR with periodontal conditions. CFTR expression in gingival biopsies from five periodontally healthy subjects and ten subjects with chronic periodontitis and in the RHGE (reconstituted human gingival epithelia) was detected by immunohistochemistry, whereas its expression in gingival biopsies was analysed by immunofluorescence staining. CFTR mRNA was analysed by reverse transcription-PCR. CFTR mRNA was detected in human gingival epithelia and RHGE. CFTR protein was detected in gingival biopsies from both healthy subjects and individuals with periodontitis and in RHGE. In healthy subjects, CFTR expression was mainly confined to the granular and spinous layers of epithelia and localized on the cell membrane. In patients with periodontitis, CFTR was detected in all layers of epithelia and the underlying connective tissues. The mean CFTR expression levels in periodontitis patients were significantly higher than those in healthy subjects. The present study for the first time showed the expression and localization of CFTR in human gingival epithelia. Elevated CFTR expression in periodontitis subjects implies the possible involvement of CFTR in periodontal disease pathogenesis. Further study is warranted to confirm the present findings.