The trends and current incidence of Creutzfeldt-Jakob disease (CJD) was examined by using a unique and potentially highly sensitive source for case ascertainment. We analyzed death certificate information for 1979–1990 from US multiple-cause-of-death mortality data, compiled by the National Center for Health Statistics, Centers for Disease Control and Prevention. We evaluated death certificate data for US residents for whom CJD was listed as one of the multiple causes of death on the death certificate (046.1) from the International Statistical Classification of Diseases, Injuries, and Causes of Death (9th revision). Age-adjusted and age-specific CJD death rates by gender, race, and region were calculated to measure the disease incidence because of the rapidly fatal course of the disease for most patients with CJD. We identified 2,614 deaths with CJD listed on the death certificates. The average annual age-adjusted mortality rate was 0.9 deaths per million persons (range 0.8–1.1). The mean age at death was 67 years. CJD-related deaths were uncommon among persons younger than 50 years of age (4.3% of all deaths). The highest average annual mortality rate was for those persons aged 70–74 years (5.9 deaths per million persons). A slight majority (53.0%) of the deaths was in females, but the age-adjusted mortality rate was 1.2 times higher for males. Most deaths (94.8%) were in whites; the mortality rate for blacks was only 40% of that for whites. The age-adjusted CJD mortality rate in the United States is similar to published estimates of the crude incidence of CJD worldwide. Annual review of national multiple-cause-of-death data may provide an efficient and cost-effective method to monitor the incidence of CJD in the United States. The relative paucity of cases among blacks requires further study to rule out detection biases, but may reflect, in part, differences in genetic and/or environmental factors.