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One-hundred sixty-four Cayapa Indians living in the Esmeraldas Province (northwest Ecuador) were studied for several erythrocyte genetic markers (ACPI, ADA, AK1, CA2, ESD, GLOl, G6PD, PGD, PGM1 subtyping and thermostability, PGM2, SODA, and HB). The Cayapa show allele frequencies typical of those of South American Indians. The absence of the CA2*2, G6PD*A, G6PD*A—, HBB*S, and HBB*C alleles and the low PGM1*1A and PGM1*2A and high PGM1*IB allele frequencies indicate that very little (no more than 2%), if any, genetic admixture has occurred with the black community living in the same area. Correspondence analysis was used to study the genetic relationships between the Cayapa and other linguistically defined Amerind populations and between the Amerinds and the other two native American groups, the Na-Dene and Eskimo-Aleut. The results of this analysis, obtained on the basis of some erythrocyte and serum markers and some blood group systems, show (1) the close affinity between the Cayapa and other South American populations, (2) the absence in the Amerind group of a clear-cut correspondence between linguistic classification and genetic relatedness, and (3) the evident distinctiveness of the Amerinds from other native American people.