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Three DNA polymorphisms (Xbal, EcoRl, and Ins/Del) of the apolipoprotein B (APOB) gene and the Cfol polymorphism of the APOE gene were investigated in a sample of 96 Cayapa Indians from Ecuador. The frequencies of the X + (0.182),/?+ (1.000), and Del alleles (0.432) at the three APOB sites were found to be higher than and to differ significantly from those reported for East Asians. No comparisons could be made between the Cayapa and other native Americans because of the lack of data on these sites. We observed in our sample that, like native American populations but unlike East Asians, the APOE allele frequencies were characterized by the absence of the APOE*2 allele and by a high frequency of the APOE*4 allele (0.280). Besides a probable drift effect, the high APOE*4 value was tentatively attributed to an effect of selection. Because this allele enhances the absorption of cholesterol by the intestine, it could confer an advantage to carriers in an unfavorable environment (i.e., diet poor in cholesterol).