The occurrence of Creutzfeldt-Jakob disease (CJD) among American Indians and Alaska Natives in the United States was evaluated using national multiple cause-of-death data and medical information obtained from state health departments. Twelve CJD deaths were identified for 1981 through 2002, and the average annual age-adjusted death rate was 0.47 per million population. This rate was significantly lower than that for whites and similar to the rate for African Americans.