There have been reports of nonrandom mating (negative-assortative mating) or preference for individuals of different major histocompatibility complex (MHC) genotypes in both mice and humans. We have examined the association of HLA-A and HLA-B genotypes, both for each locus by itself and for two-locus genotypes, in mates of 194 couples from 11 South Amerindian tribes. The proportion of couples sampled averaged >50% of the total matings with progeny for 10 of the tribes. In nearly all cases, HLA-sharing proportions were very close to those expected from random mating, suggesting strong negative-assortative mating for MHC is not present in these South Amerindians.