A myoblast clone, G6, was obtained from thigh muscle of an 11 week old human fetus, and used to examine the effect of platelet-derived growth factor (PDGF) on cell multiplication and differentiation. G6 myoblasts showed extensive fusion, and expressed creatine phosphokinase activity and muscle specific gene mRNA (myosin heavy chain, alpha-actin) when switched to a differentiation medium. The cells expressed PDGF beta-receptor mRNA, and bound 125I-PDGF-BB specifically. Expression of PDGF beta-receptors declined during in vitro differentiation. Relative levels of transcripts for the myogenic regulatory factors Myf4 (myogenin), Myf5, and Myf6 (MRF4) increased during the differentiation process, whereas Myf3 (MyoD1) was preferentially expressed in undifferentiated myoblasts. Treatment of the myoblasts with PDGF-BB increased DNA synthesis and cell density. Myogenic differentiation, analyzed as number of nuclei present in myotubes and expression of creatine phosphokinase and myosin heavy chain, was partly inhibited by the presence of PDGF-BB in the differentiation medium. PDGF-BB may, therefore, have the potential of regulating human muscle development and muscle regeneration.