Chronic renal failure is associated with a 20-fold increased risk of cardiovascular mortality, in part due to accelerated atherosclerosis. Hyperhomocysteinemia (HHCy) is common in patients with chronic renal failure. It has been established that HHCy is an independent and graded risk factor for atherosclerosis, though the mechanisms responsible for it remain obscure. Using the cardiovascular cDNA microarray approach, we screened the expression of 600 cardiovascular relevant genes in human umbilical endothelial cells and identified a number of homocysteine-modulated genes. These differentially displayed genes were classified according to the functional outcome of their encoded proteins: endothelial motility cluster, signaling cluster, and lipid metabolism cluster. The results may be relevant to understanding the mechanisms underlying the pathophysiological effects of HHCy, particularly those leading to endothelial dysfunction and the pathogenesis of atherosclerosis.