Reports documented a higher frequency of apolipoprotein E (apoE) allele epsilon 4 among mothers of children diagnosed with Down syndrome. We studied the prevalence of apoE alleles among 56 conceptuses with trisomy 13, trisomy 18, or trisomy 21. The presence of the 3 most common apoE alleles (epsilon 2, epsilon 3, epsilon 4) was determined by polymerase chain reaction-restriction fragment length polymorphism, and trisomy status was detected by fluorescent polymerase chain reaction followed by DNA fragment analysis and by conventional cytologic methods. We found no significant difference in the distribution of apoE alleles in the group of trisomy 21 fetuses compared with samples from healthy blood donors. The odds of having trisomy 18 for the apoE epsilon 4 group was 3-fold as high as for apoE epsilon 3 allele compared with the healthy control group. Furthermore, a statistically significant association was found for those with trisomy 18 and apoE epsilon 4, while for those with trisomy 13 and apoE epsilon 4, the test showed no significant association. The observed apoE allele epsilon 3 frequencies among patients with Down syndrome and healthy control subjects may help explain and support previous work that did not find high rates of atherosclerosis among these persons. The role of apoE alleles in the development of trisomies needs further study.