The carotid artery shows a common response to many forms of injury, including a rapid activation of smooth muscle cell (SMC) proliferation in the media and migration of SMCs into the intima to form a neointima. Platelet-derived growth factor (PDGF) is believed to play a role in this response to injury, but it has proven difficult to distinguish whether it is stimulating cell migration or cell proliferation, and whether the action is direct or indirect. To determine this, we created chimeric mice composed of both wild-type (WT) and marked PDGF receptor beta (PDGFRbeta)-deficient cells, and determined the consequences of PDGFRbeta expression for SMC participation in response to ligation of the left common carotid artery. The proportion of PDGFRbeta-/- SMCs increased 4.5-fold in the media and decreased 1.8-fold during formation of the neointima, consistent with migration of WT SMCs out of the media and into the intima, leaving the PDGFRbeta-/- cells behind. The fibrotic reaction in the adventitia, which does not involve cell migration, did not result in any change in relative abundance of WT and PDGFRbeta-deficient fibroblasts. We conclude that the most significant direct role of PDGFRbeta is to mediate responses that involve cell migration rather than proliferation.