Ataxia-telangiectasia (AT) is an autosomal recessive neurological syndrome of considerable interest because homozygotes are highly predisposed to cancer. Vigorous casefinding in the United States in 1970-72 and 1980-84 identified 231 white, 29 black, and three Oriental AT cases that provide information about the incidence and gene frequency of AT. White patients identified in this study were born at the rate of 3.0 per million live births in the US in the years 1965-69. The highest observed incidence was in the state of Michigan for 1965-69, where identified white AT patients were born at the rate of 11.3 per million births. Based on the incidence data, the minimum frequency of a single hypothetical AT gene in the US white population was estimated to be. 0017. Pedigree analysis, which estimates the gene frequency from the proportion of affected close blood relatives of homozygous probands, estimated the most likely gene frequency to be. 007 on the assumption that AT is a single homogeneous genetic syndrome, with 95% confidence limits of. 0012-. 02. Given that complementation analysis has demonstrated the genetic heterogeneity of AT, the AT heterozygote frequency will probably fall between 0.68% and 7.7%, with 2.8% being the most likely estimate.