Platelet-derived growth factor (PDGF) and transforming growth factor-/3, (TGF-/3,), two growthregulatory peptides with opposite effects on arterial smooth muscle cell (ASMC) proliferation, were examined for their influence on the synthesis of two small chondroitin sulfate/dermatan sulfate proteoglycans (CS/DS PGs) called biglycan and decorin. Quiescent ASMCs treated with either PDGF or TGF-0] for 24 hours increased [MS] sulfate incorporation into biglycan 3.3- and 2.9-fold, respectively, whereas the incorporation of [MS] sulfate into decorin was not significantly affected. Treatment with TGF-/3, but not PDGF more than doubled the steady-state level of messenger RNA (mRNA) transcripts hybridizing to a complementary DNA (cDNA) encoding biglycan. Both growth factors had little or no effect on steady-state levels of mRNA transcripts hybridizing to a decorin cDNA. Incorporation of ["S] sulfate into biglycan glycosaminoglycan (GAG) was maximal by 12 to 18 hours after either PDGF or TGF-ft addition. Both PDGF and TGF-0, increased the molecular sizes of biglycan and decorin. This increase was a result of the synthesis of longer GAG chains substituted on the core proteins of both PGs. PDGF but not TGF-ft led to an increase or more than twofold in the ratio of 6′- to 4-sulfated disaccharides in these newly synthesized GAG chains. These results indicate that PDGF and TGF-0, have specific but different effects on the synthesis of small CS/DS PGs by monkey ASMCs in culture.