This study has identified that sympathetically mediated blood pressure regulation is reduced following ascent to high altitude. Additionally, we show that high-altitude Andean natives have reduced blood pressure responsiveness to sympathetic nervous activity (SNA) outflow compared with Nepalese Sherpa. However, basal sympathetic activity is inversely related to the magnitude of SNA-mediated fluctuations in blood pressure regardless of population or condition. These data set a foundation to explore more precise mechanisms of blood pressure control under conditions of persistent sympathetic activation and hypoxia.