We have reported previously that a chimeric platelet-derived growth factor receptor (PDGFR) possessing the ligand binding domain of the PDGFR and the intracellular domain of the PDGFR (R) was markedly more efficient than the wild type PDGFR (RWT) in its ability to enhance PDGF-A transforming activity in NIH/3T3 fibroblasts. To determine the region within the cytoplasmic domain of PDGFR that confers this higher transforming activity, we generated several additional /PDGFR chimerae. When a chimeric PDGFR possessing the first 933 amino-terminal amino acids from the PDGFR and the final 165 amino acids from the carboxyl-terminal of the PDGFR (R) was cotransfected with the PDGF-A gene into NIH/3T3 cells, it showed a similar high efficiency to enhance PDGF-A chain transforming activity as R. However, when chimeric PDGFRs in which either the kinase insert domain (RKI) or the last 79 amino acids from the carboxyl-terminal end of the PDGFR (R) were substituted into PDGFR sequences were cotransfected with PDGF-A, they showed similar low efficiencies in enhancing transforming activity as the RWT. These results predicted that the 86 amino acids following the tyrosine kinase 2 domain of PDGFR (amino acid residues 942-1027) were responsible for the higher transforming activity of PDGFR. To confirm this finding, we next constructed a chimera in which amino acid residues 942-1028 of the PDGFR (R) were substituted for those in the PDGFR. Cotransfection experiments indicated that R increased transforming activity of PDGF-A to similar extent as the R or R. Therefore, our findings define a critical domain within the noncatalytic region of PDGFR intracellular domain that confers the higher focus forming activity mediated by the PDGFR.