There is intriguing evidence associating apolipoprotein E (ApoE) with Alzheimer's disease (AD). ApoE is deposited with beta-amyloid in senile plaques and binds to beta-amyloid in vitro. We used denaturing gradient gel electrophoresis to identify ApoE epsilon 2, epsilon 3, and epsilon 4 alleles in 135 control subjects and 57 AD patients. We observed a marked increase in ApoE epsilon 4 allele frequency (0.40) in AD patients compared with control subjects (0.14) (p < 0.0001). Our independent finding of a marked association of ApoE epsilon 4 allele with AD further supports a possible role of ApoE in the pathogenesis of AD and confirms the study of Saunders et al (Neurology 1993;43:1467-1472).