Plasma volume (PV) can be modulated by altitude exposure (decrease) and periods of intense exercise (increase). Cycle racing at altitude combines both stimuli, although presently no data exist to document which is dominant. Hemoglobin mass (Hbmass), hemoglobin concentration ([Hb]), and percent reticulocytes (%Retics) of altitude (ALT; n = 9) and sea-level (SL; n = 9) residents were measured during a 14-day cycling race, held at 1,146-4120 m, as well as during a simulated tour near sea level (SIM; n = 12). Hbmass was assessed before and on days 9 and 14 of racing. Venous blood was collected on days 0, 3, 6, 10, and 14. PV was calculated from Hbmass and [Hb]. A repeated-measures ANOVA was used to assess the impact of racing at altitude over time, within and between groups. [Hb] decreased significantly in all groups over time (P < 0.0001) with decreases evident on the third day of racing. %Retics increased significantly in SL only (P < 0.0001), with SL values elevated at day 6 compared with prerace (P = 0.02), but were suppressed by the end of the race (P = 0.0002). Hbmass significantly increased in SL after 9 (P = 0.0001) and 14 (P = 0.008) days of racing and was lower at the end of the race than midrace (P = 0.018). PV increased in all groups (P < 0.0001). Multiday cycle racing at altitude induces hemodilution of a similar magnitude to that observed during SL racing and occurs in nonacclimatized SL residents, despite an altitude-induced increase in Hbmass. Osmotic regulatory mechanisms associated with intense exercise appear to supersede acute enhancement of oxygen delivery at altitude.