Anatomical closure of the ductus arteriosus (DA) requires normally quiescent smooth muscle cells (SMC) to migrate out of the muscle media into the subendothelial space, forming intimal mounds that eventually coalesce to occlude the vessel's lumen. Transforming growth factor-B, (TGF{31)' a potent modulator of vascular SMC migration, is found in the wall of the closing DA. We examined the effect of TGF{31 on the migration of fetal lamb DA-SMC. Although TGF{31 has been shown to be a chemoattractant for other mesenchymal cells, it had no chemotactic effect on DA-SMC; furthermore, TGF{31 did not enhance the migration of DA-SMC (as has been reported for aortic SMC). Rather, incubating DA-SMC with TGF{31 for 22 h decreased the rate of migration of SMC on extracellular matrix substrata composed of fibronectin, vitronectin, laminin, and collagen I and IV. Exposure of DA-SMC to TGF{31 was associated with an increase in the formation of focal adhesion plaques (tight associations between the cells' surface and extracellular matrix). DA-SMC use integrin receptors to attach to and migrate on extracellular matrix components. The decrease in DA-SMC migration was not associated with a significant change in the profile of integrin receptors Closure of the DA is a necessary adaptation to extrauterine life . Term infants functionally close their DA within the first several hours of life , followed by vessel w all reorganization and permanent anatomical clo sur e. Preterm infants, however, frequently show initial constriction of the muscular media (functional closure), but fail to initiate vessel wall remodeling, leading to patency of the DA and its associated morbidity.DA remodeling is dependent upon the migration of SMC from the muscle media into the subendothelial space; this forms the intimal mounds nec essary for obliteration of the vessel 's lumen and permanent anatomical closure. For migra-