We questioned the assumption that polycythemia is essential for adaptation to chronic hypoxia. Thus, the objective of our study was to determine if anemic Epo-TAgh mice could survive in hypoxia despite low oxygen carrying capacity. We explored the possibility that ventilatory acclimatisation is involved in the strategy used by anemic transgenic mice to adapt to chronic hypoxia. Epo-TAgh and Wild Type mice were exposed during 2 weeks at a barometric pressure of 450 Torr. After 1, 5 and 14 days of exposure, ventilation at different inspired oxygen fraction was measured in both groups. Ventilation during acclimatisation to hypoxia was significantly greater in Epo-TAgh than in Wild Type. The difference was mainly due to a higher tidal volume that could explain a higher arterial PO2 in Epo-TAgh mice. Epo-Tagh mice did not develop right ventricle hypertrophy after 2 weeks of exposure to hypoxia while Wild Type did. Hemoglobin concentration was 60% lower in anemic mice versus Wild Type after acclimatisation. In conclusion, ventilatory acclimatisation contributed to the adaptation of Epo-Tagh mice in chronic hypoxia despite low arterial oxygen carrying capacity. © 2005 Elsevier B.V. All rights reserved.