The effect of specifically derivatized dextrans, with or without antiproliferative activity on smooth muscle cells (SMC), was investigated on type I and type III collagen biosynthesis and mRNA levels in post-confluent SMC cultures. Our results indicate that dextran derivatives decreased total protein and collagen synthesis independently of their antiproliferative activities. However, the most substituted dextran, the one exhibiting the strongest antiproliferative activity towards SMC, was the most active in modulating type III collagen expression. In addition, only the two dextran derivatives bearing benzylamide groups inhibited collagen excretion.