Exposure to arsenic (As) has been associated with a number of diseases such as cancers, cardiovascular diseases (CVD), and neurological disorders. To explore the possible underlying epigenetic mechanisms, a nested case-control study was conducted within the Coronary Artery Risk Development in Young Adults (CARDIA) study by randomly selecting 46 non-smoker and non-diabetic White participants with low (N=23) and high (N=23) As exposure based on toenail total As measures at examination year 2. We conducted methylomic profiling of white blood cell (WBC) DNA collected at examination year 15 using the Illumina HumanMethylation450 BeadChip, and performed association tests using multiple linear regression models adjusting for age, sex, and estimated WBC proportions. We observed 22 CpG sites with methylation levels associated with high As exposure at a nominal significance level of 10(-4). However, the statistical significance disappeared after correction for multiple testing. Some genes annotated by these 22 CpG sites are known to be involved in As-associated diseases. Replication in larger samples of individuals with low levels of As exposure will be required.