Elevated levels of transforming growth factor-β (TGF-β) within the vessel wall have been implicated in restenosis following balloon angioplasty (1). We have previously shown that migration of adventitial fibroblasts contributes to arterial remodelling and neointima formation elicited by vascular injury (2). Migration of vascular cells is partly regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), and a balance between MMP and TIMP expression contributes to arterial remodelling under physiological and pathological conditions (3). TGF-β1 is known to modulate MMP and TIMP activity thus may facilitate adventitial cell migration (4). The present study has utilised vascular gene transfer of smad7, an endogenous inhibitor of TGFβ signalling (5), to investigate whether antagonism of TGF-β1 alters luminal loss and adventitial cell migration following balloon injury in rat carotid arteries. Rats were anaesthetised with intraperitoneal administration of ketamine hydrochloride (72 mg/kg) and xylazine hydrochloride (5 mg/kg) before adenoviral vectors coordinating expression of nuclear β-galactosidase (β-gal) or smad7 were applied to the perivascular surface of left common carotid arteries. Balloon catheter mediated carotid artery injury was performed 4 days after gene transfer and animals humanely killed 3, 7 and 14 days later. Migration of adventitial fibroblasts was determinied by tracking β-gal labelled cells in histological sections. Vascular collagen content was assessed by picrosirius red staining and expression of smooth muscle α-actin, MMPs and TIMPs were determined by immunohistochemistry. Uninjured arteries only expressed adventitial β-gal positive cells; however, following balloon injury, β-gal positive cells were observed within the medial layer of vessels and contributed to the population of cells within the neointima at 7-14 days. Overexpression of smad7 with β-gal resulted in a significant reduction in the number of β-gal labelled cells in the neointima (14±4 vs 38±5%, mean±S.E.M., n=12, p<0.01, Student's t test), concomitant with reduced luminal loss (0.34±0.02 vs 0.27±0.02 mm², n=12, p<0.01) and decreased adventitial α-actin expression and collagen content (64±3 vs 51±6%, n=12, p<0.01) compared with controls. Levels of MMP-2 were decreased and TIMP-1 expression enhanced in arteries transfected with smad7 compared to those overexpressing β-gal only. These findings may partly explain the beneficial effects of antagonizing TGF-β1 signalling by smad7 overexpression on attenuating adventitial cell migration and arterial remodelling following vascular injury.