A HIGH concentration of serum lipoprotein(a) is a risk factor for atherosclerosis^1–3. Lipoprotein(a) consists of low-density lipoprotein with the additional protein component, apolipoprotein(a), a homologue of plasminogen⁴. Lipoprotein(a) and apolipoprotein(a) enhance proliferation of human vascular smooth muscle cells (hVSMCs) in culture by inhibiting activation of plasminogen to plasmin, thus blocking the proteolytic activation of transforming growth factor-β (TGF-β)⁵, an autocrine inhibitor of hVSMC proliferation^5,6. The hypothesis that this pathway is a key step in atherogenesis⁵ is tested on transgenic mice expressing the human apolipoprotein(a) gene. We show here that the activation of TGF-β is inhibited in the aortic wall and serum of mice expressing apolipoprotein(a), as a consequence of apolipoprotein(a) inhibition of plasminogen activation. These effects are closely correlated with VSMC activation.