2002). Importantly, this condition highlights the importance of HIF signaling not only for EPO regulation, but also in the regulation of systemic oxygen delivery more broadly. Patients with Chuvash polycythemia display elevated minute ventilation and pulmonary artery pressures at baseline, and profoundly enhanced pulmonary vascular, ventilatory and cardiac responses to acute hypoxia (Bushuev et al. 2006; Smith et al. 2006, 2008b), a phenotype reminiscent of that seen in lowlanders acclimatized to the hypoxia of high altitude. This evidence concerns the gene EPO and Chuvash polycythemia.