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Altitude acclimatization is associated with a rapid increase in hematocrit. The time course and the contribution of the red cell volume expansion are not clear. The purpose of the present meta-analysis was to explore how much altitude exposure is required to induce polycythemia in healthy lowlanders.A systematic review was performed of 66 published articles (including 447 volunteers) identified through literature search. We performed a mixed-model random-effects meta-analysis and a Monte Carlo simulation on the extracted data.The following results were obtained in this study: 1) the red cell volume expansion for a given duration of exposure is dependent on altitude (P < 0.0001), that is, that the increase in red cell volume was accelerated at higher altitudes; and 2) the extent of the erythropoietic response depends on the initial red cell volume (P < 0.0001). It seems that exposure time must exceed 2 wk at an altitude of more than 4000 m to exert a statistically significant effect. At lower altitudes, longer exposure times are needed with altitudes lower than 3000 m not yielding an increase within 4 wk.Red cell volume response to hypoxia is generally slow, although it accelerates with increasing altitude. This, in combination with a dependency on initial red cell volume, suggests that, for example, athletes may need to spend more time at altitude to see an effect on red cell volume than commonly recommended.