We measured the hematological response to ∼6 wk exposure to an altitude of 5,400 m in Sherpa highland natives and Nepalese lowlanders. While the increase in hemoglobin concentration at high altitudes tended to be smaller in Sherpas than in lowlanders, the two groups experienced a similar reduction in plasma volume and increase in hemoglobin mass. We conclude that the hematological response of Sherpas to high-altitude exposure does not fundamentally differ from that of lowlanders.