AbstractPlatelet-derived growth factor (PDGF) consists of disulfide-linked homo-or heterodimers of A and B chains. mRNA encoding the A chain (PDGF-A) occurs in two versions that differ by the presence or absence of a single short exon. These alternatively-spliced mRNAs encode polypeptides that differ in length by fifteen amino acids. The longer isoform (PDGF-AL) possesses a highly basic carboxy-terminal extension that is responsible for retaining PDGF-ALhomodomers at the cell surface after secretion, while homodimers of the shorter isoform (PDGF-AS) are released into the extracellular medium. We have investigated the mechanism by which PDGF-ALremains in association with the cells that produce it. We expressed epitope-tagged versions of PDGF-ALand PDGF-ASin Cos cells and compared their intra-and extracellular distributions by immunofluorescence microscopy. PDGF-AL, but not PDGF-ASwas detected on and around cells in a diffuse pattern suggesting association with the extracellular matrix (ECM). Metabolically radiolabeled PDGF-AL, but not PDGF-AS, could be eluted from ECM preparations by washing in high salt. Moreover, PDGF-ALbound reversibly to heparin-Sepharosein vitroat physiological salt concentrations, eluting at a salt concentration around 0.5 M. PDGF-ASdid not bind to heparin under the same conditions. Thus, PDGF dimers that contain PDGF-ALmay remain immobilized near the cells that secrete them by virtue of binding to heparin-like constituents of the ECM.