The effect of low M(r) heparin fragments (CY222) and fetal calf serum (FCS) on the level of fibronectin and fibrillar collagen mRNAs was investigated in smooth muscle cells (SMC) in culture. In the absence of FCS, addition of CY222 (100 micrograms/10(6) cells) to postconfluent early passage SMC resulted in a decrease in mRNA level of type III collagen. In contrast, mRNA levels coding for type I collagen, fibronectin and GAPDH (used as control of cellular activity) were not modified. Addition of 5% FCS (without CY222) to the culture medium did not affect mRNA levels of type I and type III collagens nor that of GAPDH. The level of fibronectin mRNA, however, increased in the presence of 5% FCS. In the presence of both 5% FCS and CY222, we observed a decrease in type III collagen mRNA and fibronectin mRNA levels (this level remained, however, above the control value without FCS and the level with CY222 alone). Our results demonstrate that low M(r) heparin fragments can modulate the steady-state levels of type III collagen and fibronectin mRNAs.