INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.