HLA-G (human leukocyte antigen-G) plays an important role in the modulation of the maternal immune system during pregnancy. HLA-G alleles presenting a 14-bp insertion at exon 8 have been associated with decreased messenger RNA levels, preeclampsia, and miscarriages. This suggests that natural selection may exert a strong influence against the insertion allele in isolated populations. DNA samples from 384 Amazonian Indians spread across seven isolated tribes were evaluated for the 14-bp polymorphism. The insertion frequency (38.54%) was somewhat low. The Ewens-Watterson's neutrality test showed a slight trend toward balancing selection operating at this locus but no correlation between the 14-bp locus and fertility data was found. To sum up, no definitive evidence was obtained indicating that the 14-bp frequencies in Amerindians depart from neutrality.