Despite decades of research, the magnitude and time course of hematologic and plasma volume (PV) changes following rapid ascent and acclimation to various altitudes are not precisely described. To develop a quantitative model, we utilized a comprehensive database and general linear mixed models to analyze 1055 hemoglobin ([Hb]) and hematocrit (Hct) measurements collected at sea level and repeated time points at various altitudes in 393 unacclimatized men (n=270) and women (n=123) who spent between 2 hours and 7 days at 2500-4500 m under well-controlled experimental conditions. The PV change (PV) was calculated from Hb and Hct measurements. The results are: 1) PV decreases rapidly (~6%) after the 1^st day at 2500 m and [Hb] and Hct are increased by 0.5 g/dl and 1.5 points, respectively, 2) PV decreases an additional 1% and [Hb] and Hct increase an additional 0.1 g/dl and 0.2 points for every 500 m increase in elevation above 2500 m after the 1st day, 3) PV continues to decrease over time at altitude but the magnitude of this decrease and subsequent increase in [Hb] and Hct levels is dependent on elevation and sex, 4) individuals with high initial levels of [Hb] and Hct and older individuals hemoconcentrate less at higher elevations. This study provides the first quantitative delineation of PV and hematological responses during the first week of exposure over a wide range of altitudes and demonstrates that absolute altitude and time at altitude, as well as initial hematologic status, sex, and age impact the response.