Smooth muscle cell (SMC) markers of differentiation are known to down-regulate in late stages of atherosclerosis, a process known as dedifferentiation. However, it is unknown whether, as with endothelial cells, any regional differences in SMC gene expression exist during early stages of atherosclerosis. From various methods of microdissection, optimal techniques were identified for harvesting SMC from distinct regions of the mouse aorta. Several internal control genes were tested for real time RT-PCR, and beta-2-microglobulin was most reliable. No detectable differences in SMC marker gene expression exist at baseline between three different regions of the mouse aorta. Surprisingly, temporal increases in SMC marker gene expression were observed in areas of high probability for subsequent lesion formation. These changes occurred in the presence of only limited inflammatory cell infiltration and lipid deposition. These observations may indicate that dedifferentiation of SMC during atherosclerosis is not an early event in disease progression.