THE ESTIMATED TWO MILLION American Indians and Alaska Natives, while sharing certain genetic traits, belong to groups with distinct social, cultural, political, and biomedical attributes. They share with certain other ethnic minorities high poverty rates, low educational attainment, increased susceptibility to certain diseases, and elevated mortality rates. Hypertension has been reported less frequently among American Indians compared to other U.S. groups, but is increasing in frequency, is strongly associated with obesity and diabetes, and is synergistically associated with diabetes in the etiology of end-stage renal disease. The first priority for dealing with hypertension among American Indians is to maximize efforts toward control. The Indian Health Service (IHS) provides such an opportunity, which is not as readily available to other minorities. In addition to controlling hypertension, areas of fruitful investigation include studies relating hypertension to acculturation, physiology of peripheral adrenergic vasoreceptors, salt and water metabolism, and prevention or amelioration of end-stage renal disease. Understanding some of these basic processes will prove valuable for American Indians and Alaska Natives as well as the entire population.