The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study is a national, population-based, longitudinal study of 30,000 African-American and white adults aged ≧45 years. The objective is to determine the causes for the excess stroke mortality in the Southeastern US and among African-Americans. Participants are randomly sampled with recruitment by mail then telephone, where data on stroke risk factors, sociodemographic, lifestyle, and psychosocial characteristics are collected. Written informed consent, physical and physiological measures, and fasting samples are collected during a subsequent in-home visit. Participants are followed via telephone at 6-month intervals for identification of stroke events. The novel aspects of the REGARDS study allow for the creation of a national cohort to address geographic and ethnic differences in stroke.