SummaryCardiovascular disease (CVD) is reportedly less common in high‐altitude native populations than in lowlanders. To some extent, this is due to cultural and demographic factors; however, increased cardiovascular efficiency contributing to hypoxia adaptation may also be involved. Numerous genetic variants have been associated with cardiovascular health. If the decreased incidence of CVD in modern high‐altitude populations reflects selective pressures having favoured the transmission of these alleles in their antecedents, it would be expected that these alleles would be more common in highlanders than in lowlanders. We tested this hypothesis by determining the allele frequencies of five polymorphic loci in genes encoding components of the renin‐angiotensin system (RAS) that have alleles associated with hypertension and cardiovascular disease in a high‐altitude native Andean population, Quechua from the Peruvian altiplano, and in a lowland Amerindian population, Maya from the Yucatan peninsula. The polymorphisms examined were 1) the insertion/deletion polymorphism in intron 16 of the angiotensin converting enzyme (ACE) gene; 2) the A/G2350 transition (ACE‐8) in intron 17 of the ACE gene; 3) the A/C1166 transversion in the 3′ untranslated region of the angiotensin II receptor (type 1) gene (AGTR1); 4) the G/AI9–83 transition in intron 8 of the renin gene (REN); and 5) the T/C704 (Met235Thr) transition mutation in angiotensinogen (AGT).There was no evidence for an over‐representation of the RAS alleles associated with cardiovascular fitness in the high‐altitude Amerindian population when compared to the lowland Amerindian population.