The mechanism of diabetic macroangiopathy was studied from the view point of phenotypic change of aortic smooth muscle cells (SMC). The growth rates of cultured SMC of diabetic rats or rabbits were higher than those of non-diabetic animals (controls). This difference of the growth responses was observed specifically with platelet-derived growth factor (PDGF). Of the three PDGF dimers, PDGF-AB heterodimer (PDGF-AB) and PDGF-BB homodimer (PDGF-BB) stimulated growth of diabetic SMC more than that of control SMC but PDGF-AA homodimer (PDGF-AA) did not. The binding of 125I-PDGF to the diabetic SMC was greater than that to control SMC. This was due to increase in the number of cell surface receptors for PDGF. On in vitro culture, SMC from diabetic rats expressed more PDGF beta-receptor mRNA than SMC from non-diabetic rats. Moreover, in vivo, the aortic media of diabetic rabbits expressed PDGF beta-receptor mRNA, but that from non-diabetic rabbits did not. Thus diabetic SMC over-react on PDGF stimulation through over-expression of the PDGF beta-receptor gene. The significance of this fact in development of diabetic macroangiopathy is discussed.