The relationships that exist between proliferative states and proteoglycan (PG) synthesis have been examined in monkey aortic smooth muscle cells in culture. These cells were made quiescent in medium containing low serum (0.1%) and stimulated to divide by addition of either nanogram quantities or platelet-derived growth factor (PDGF) or medium containing 5% serum. Incorporation of [35S]sulfate into PG was increased during the first 24 h of growth stimulation, and this increase appeared to be principally in the large chondroitin sulfate proteoglycan (CSPG). Furthermore, addition of p-nitrophenyl beta-D-xyloside, which perturbs PG metabolism, inhibits cells from proliferating, suggesting that PG may be involved in facilitating cell division. Inhibition of cell proliferation by heparin and/or TGF-beta also causes elevated levels of 35S-sulfate incorporation into PG by these cells. These studies indicate that proteoglycan metabolism is modulated as a function of the growth of arterial smooth muscle cells; however, it is still uncertain whether PG play a direct or indirect role in the control of cell growth.