Six blood group antigens (ABO, RH, MNS, KK, KP, FY) and five plasma proteins (HP, GC, APOA4, FXIIIB, C1R) were typed in 790 individuals, and 12 mtDNA RFLP and deletion polymorphisms were typed in 657 individuals from the San Luis Valley, Colorado. The 790 nuclear typings were conducted on 399 Anglos and 391 Hispanics, while the 657 mitochondrial haplotypes were generated from 207 Anglos and 450 Hispanics. Chakraborty's ADMIX2 FORTRAN program was used to estimate the average Amerindian admixture using all nuclear loci simultaneously. Since there is no recombination in mtDNA, the sum of the frequencies of the Amerindian/Asian-specific mitochondrial haplotypes represents the level of Amerindian admixture. The nuclear estimates of Amerindian admixture were 33.15 +/- 2.41% for the Hispanics and 9.72 +/- 1.90% for the Anglos, while the strictly maternally inherited mtDNA estimates of Amerindian admixture were 85.11% for the Hispanics and 0.97% for the Anglos. This dramatic difference in estimated levels of admixture between the biparentally derived nuclear estimates and the uniparentally derived mtDNA estimates is indicative of past directional matings between Hispanic males and Amerindian females.