The synthesis of hyaluronic acid (HA) and sulphated glycosaminoglycans (S-GAGs) by cultured human aortic smooth muscle cells (SMC) was measured in the presence of human sera with high LDL-cholesterol concentration (type IIA hyperlipoproteinemic patients) or high HDL-cholesterol concentration (marathon runners and lumberjacks). In addition, the effect of some hormones on GAG-synthesis was studied. As compared to normolipidemic controls, type IIA hyperlipoproteinemic sera decreased markedly the synthesis of HA without affecting the synthesis of S-GAGs. On the contrary, sera with high HDL-cholesterol concentration decreased the synthesis of S-GAGs causing a decrease in S-GAGs/HA ratio. Cortisol in concentrations slightly above the physiological level inhibited the synthesis of HA and increased the S-GAGs/HA ratio. Insulin, and interestingly also sex hormones (estradiol, progesterone, testosterone) had no clear effect on GAG-synthesis. It is known that there is an increased S-GAGs/HA ratio in early atherosclerotic lesions. Our results suggest that the determination of this ratio in SMC cultures provides an useful method of studying the atherogenity and antiatherogenity of various sera and hormones.