Epithelial damage is an important pathophysiological feature of asthma. Bronchial epithelium damage results in release of growth factors such as TGF-₁ that may affect epithelial cell proliferation. The objective of our study is to evaluate the importance of TGF-₁ in regulating epithelial cell repair in asthma. We evaluated the effect of TGF-₁ on EGF-induced proliferation and downstream signalling in epithelial cells obtained from asthmatic subjects compared to cells from healthy subjects. Cell proliferation was evaluated by BrdU incorporation. EGFR, MAPK, TGF- receptors, Smads, SARA and cyclin-dependant kinase inhibitors were evaluated by Western Blot. TGF-₁ and receptor expression were measured by RT-PCR and by ELISA. Proliferation of epithelial cells at baseline and after EGF stimulation was significantly reduced in cells derived from asthmatic subjects compared to cells obtained from healthy controls. EGF induced ERK1/2 phosphorylation was reduced in epithelial cells from asthmatics compared to cells from healthy controls. This was paralleled with a reduced EGFR phosphorylation. Addition of TGF-₁ significantly decreased EGF-induced cell proliferation. TGF-₁ production was higher in asthmatic epithelial cells compared to normal cells. This was supported by a high expression of pSmad 3 and SARA in cells derived from asthmatics compared to normal subjects. Cycline-dependent kinase inhibitors were highly expressed in asthmatic compared to normal cells. Inhibition of TGF-₁ signalling in asthmatic epithelial cells restored EGFR, ERK1/2 phosphorylation and cell proliferation induced by EGF. Our results suggest that TGF- restrains EGFR phosphorylation and down-stream signalling in bronchial epithelial cells.