AbstractPlatelet-derived growth factor (PDGF) is a disulfide-bonded antiparallel dimer of A-and B-polypeptide chains. Each subunit contains two loops (loops 1 and 3) which point in the same direction, and which are located close to a region (loop 2) from the other subunit of the dimer. Previous studies have shown that epitopes in loops 1 and 3 are important for binding to PDGFα-andβ-receptors. The aim of the present investigation was to determine the importance of loop 2 for receptor interactions. PDGF A-and B-chain cDNA:s were mutated in the loop 2 regions and transfected into COS cells. Analyses of conditioned media of such cell cultures revealed that PDGF B-chain mutated in the loop 2 region lost its ability to compete with125I-PDGF for binding to PDGFβ-receptors, but retained 2–5% of its binding ofα-receptors. The A-chain binds only toα-receptors; 2–5% of this binding was also retained after mutation of the loop 2 region. In conclusion, the loop 2 region of PDGF is important for receptor binding, but appears to be more important for binding to the PDGFβ-receptors than to theα-receptors.