OBJECTIVE: To determine the prevalence of restless legs syndrome (RLS) in native South Americans and identify the impact of geographic location. PARTICIPANTS AND METHODS: Am epidemiological telephone survey of RLS symptoms involving natives from coastal and mountainous areas was performed during July 2, 2004, through September 28, 2004. The process consisted of 2 phases: the creation of the epidemiological instrument and the telephone survey. RESULTS: Five hundred adults, 250 from the mountainous regions and 250 from the coastal region (190 men and 310 women; age range, 25-85 years) were interviewed and subsequently divided on the basis of International Restless Legs Syndrome Study Group criteria into those who had RLS (RLS+ group) and those who did not (RLS- group). Ten (2.0%) had RLS. The overall rate of RLS in adults living in the mountainous region at 2816 m above sea level (3.2% [8/250]) was significantly higher than that for adults living in the coastal region at 4 m above sea level (0.80% [2/250]; P=.002). The mean age of the RLS+ group was 49.5 years (SD, 15.20 years; range, 25-35 years). CONCLUSION: Native South American adults have a prevalence of RLS well below that reported in populations with European ancestry but similar to that in Asian and Turkish populations. Furthermore, in Ecuador, geographic differences were identified in areas of similar population density.