Orthostatic tolerance is a measure of the ability to prevent hypotension during gravitational stress. It is known to be dependent on the degree of vasoconstriction and the magnitude of plasma volume, but the possible influence of packed cell volume (PCV) is unknown. High altitude residents have high haematocrits and probably high packed cell volumes. However, it is not known whether plasma volume and blood volume are affected, or whether their orthostatic tolerance is different from low attitude residents. In this study we determined plasma volume, PCV and orthostatic tolerance in a group of high altitude dwellers (HA), including a subgroup of highland dwellers with chronic mountain sickness (CMS) and extreme polycythaemia. Plasma volume and PCV were determined using Evans Blue dye dilution and peripheral haematocrit. Orthostatic tolerance was assessed as the time to presyncope in a test of head-up tilting and lower body suction. All studies were performed at 4338 m. Results showed that plasma volumes were not significantly different between CMS and HA, or in highland dwellers compared to those seen previously in lowlanders. PCV and haematocrit were greater in CMS than in HA. Orthostatic tolerance was high in both CMS and HA, although the heart rate responses to orthostasis were smaller in CMS than HA. Orthostatic tolerance was correlated with haematocrit (r = 0.57, P < 0.01) and PCV (r = 0.54, P < 0.01). This investigation has shown that although high altitude residents have large PCV, their plasma volumes were similar to lowland dwellers. The group with CMS have a particularly large PCV and also have a very high orthostatic tolerance, despite smaller heart rate responses. These results are compatible with the view that PCV is of importance in determining orthostatic tolerance. © The Physiological Society 2004.