Evidence has been provided of enhanced epithelial transforming growth factor-beta (TGF-beta) immunoreactivity in allergic rhinitis, including correlation with intra-epithelial mast cell numbers, and the co-localisation of TGF-beta receptors to mast cells, suggesting that the epithelial expression of TGF-beta may represent an important biological process involved in either the recruitment or retention of mast cells within the epithelium in naturally occurring allergic rhinitis. In order to extend the above findings, evaluation was undertaken in whole nasal biopsies from subjects with naturally occurring allergic rhinitis, of levels of TGF-beta isotypes and receptors gene expression using real-time quantitative polymerase chain reaction (TaqMan RT-PCR), and the results compared to those for tumour necrosis factor-alpha (TNF-alpha), as a positive control. The study was also extended to evaluate gene expression for connective tissue growth factor (CTGF) and Smad proteins, as downstream markers of TGF-beta bioactivity, in the same populations. There were no significant differences between the rhinitic and non-rhinitic groups in the expression of TGF-beta isoforms or Smad-3, Smad-6 and Smad-7 proteins; however, there was increased gene expression for TGF-betaRI and TGF-betaRII along with CTGF in seasonal allergic rhinitis. TNF-alpha gene expression was also increased in seasonal allergic rhinitis, consistent with a more acute inflammatory response in this form of rhinitis. This study advances our understanding of the role of TGF-beta in the pathogenesis of the inflammatory response in allergic rhinitis.