For the establishment of a fully functional septated heart, addition of myocardium from second heart field-derived structures is important. Platelet-derived growth factors (PDGFs) are known for their role in cardiovascular development. In this study, we aim to elucidate this role of PDGF-A, PDGF-C, and their receptor PDGFR-α. We analyzed the expression patterns of PDGF-A, -C, and their receptor PDGFR-α during avian heart development. A spatiotemporal pattern of ligands was seen with colocalization of the PDGFR-α. This was found in second heart field-derived myocardium as well as the proepicardial organ (PEO) and epicardium. Mechanical inhibition of epicardial outgrowth as well as chemical disturbance of PDGFR-α support a functional role of the ligands and the receptor in cardiac development. Developmental Dynamics 238:2658–2669, 2009. © 2009 Wiley-Liss, Inc.