Atherosclerotic lesions occur as a result of excess lipid deposition within the vascular tissues. The peroxisome proliferatoractivated receptors (PPARs) present in adipose and hepatic tissues have been shown to promote fatty acid oxidation and lipid storage. An immunohistochemical assessment of PPARα and PPARγ revealed both proteins were also present in the medial and intimal layers of human arteries, predominately in regions containing smooth muscle cells. In agreement with this observation, smooth muscle cells isolated from these vessels were found by RT-PCR to express both PPARα and PPARγl. The functionality of these receptors was tested with selective PPAR agonists. Mitogenic stimulation of smooth muscle cell proliferation was blocked by 15d-PGJ₂, a PPARγ agonist, as well as by WY14643, a PPARα agonist. These data indicate PPAR activation by selective agonists could influence lesion progression directly, as well as indirectly through reductions in serum lipoprotein and triglyceride levels. (Mol Cell Biochem 246: 105–110, 2003)