DURING wound healing, migrating cells increase expression of both the vitronectin receptor (VNR) integrins¹ and plasminogen activators^2,3. Here we report that vitronectin significantly enhances the migration of smooth muscle cells (SMCs), and that the specific VNR α_vβ₃ is required for cell motility. We also show that the α_vβ₃ attachment site on vitronectin overlaps with the binding site for plasminogen activator inhibitor (PAI)-l, and that the active conformation of PAI-1 blocks SMC migration. This effect requires high-affinity binding to vitronectin, and is not dependent on the ability of PAI-1 to inhibit plasminogen activators. Formation of a complex between PAI-1 and plasminogen activators results in loss of PAI-1 affinity for vitronectin and restores cell migration. These data demonstrate a direct link between plasminogen activators and integrin-mediated cell migration, and show that PAI-1 can control cell–matrix interactions by regulating the accessibility of specific cell-attachment sites. This indicates that the localization of plasminogen activators at sites of focal contact does not initiate a proteolytic cascade leading to generalized matrix destruction, but instead is required to expose cryptic cell-attachment sites necessary for SMC migration.