Information concerning the HLA-A and -B loci was considered in relation to 3796 Amerindians living in 39 places in South America, data related to HLA-C being based on a smaller subset of 2989 persons distributed among 33 localities. Synthetic gene frequency maps were then constructed using principal-components analysis. Clearly significant longitudinal (principal component 1) and latitudinal (principal components 1, 2, and 3) clines were observed, most probably indicating ancient migration routes.