['Proliferation of smooth muscle cells (SMCs) plays an important role in vascular pathobiology, being involved in the development of coronary restenosis and atherosclerosis. The activation of nuclear proto-oncogenes appears to be a final common pathway onto which various mitogenic signals coverage. Accordingly, we attempted to determine whether the activation of the c-myc nuclear proto-oncogene is essential for human SMC proliferation and explored the possibility of inhibiting their growth using antisense oligonucleotides directed against c-myc messenger RNA (mRNA).', 'Proliferation of human SMCs was associated with an increase in c-myc mRNA expression after growth stimulation. Using 15-mer phosphorothioate oligonucleotides (oligomers), we tested their growth-inhibitory effect in SMCs in vitro. Antisense oligomers directed against the translation initiation region of the human c-myc gene exhibited a significant antiproliferative effect, whereas sense and mismatched oligomers did not inhibit the growth. The growth-inhibitory effect of c-myc antisense oligomers was dose dependent and preventable by an excess of sense oligomers. Furthermore, growth inhibition of SMCs treated with c-myc antisense oligomers was associated with a marked decrease in the c-myc mRNA level. Phosphorothioate oligomers remained stable in medium containing 20% serum and were detectable in SMCs as early as 1 hour after cell exposure. Intact oligomers rapidly accumulated intracellularly and persisted within human SMCs for at least 16 hours.'] Does downregulation of c-myc expression by antisense oligonucleotides inhibit proliferation of human smooth muscle cells?