The Subacute Sclerosing Panencephalitis Registry has compiled data from 453 instances of SSPE occurring in the United States from 1960 through 1976. The mean annual incidence during this period was 3.5 per 10 million persons under 20 years of age, 2.3 times higher for males than females, and 4.0 times higher for whites than blacks. Although the long-term pattern of incidence is unknown, the incidence of reported SSPE declined dramatically from 1970 to 1976. There are marked geographic variations of SSPE activity within the United States and also a higher incidence for children from farms (9.4 per 10 million persons under 20) compared with children from other rural domiciles (3.7 per 10 million), suburban children (2.9 per 10 million), and inner-city children (1.6 per 10 million). Available epidemiologic evidence suggests that some extrinsic factor, unrelated to measles or measles vaccine, is important in the pathogenesis of the disease.