The human venous system appears to be adapted to blood loss, since the venous distending pressure is only moderately reduced during bleeding. A rapid change from supine to upright position presents a greater challenge to the system, since a larger proportion of blood is shifted to veins below the level of the heart. The aim of this work was to study how the circulatory system copes with a progressive reduction in blood volume followed by changes in posture. Since rapid head-up tilting causes central hypovolemia, this manoeuvre might add to the effects of bleeding, jeopardizing blood pressure control. The test person is homozygote for the hemochromatosis gene, HFE, and therefore undergoes phlebotomy 2–4 times a year as a precaution against iron accumulation. On 22 of these occasions, over a 10-year period, mean arterial pressure (MAP), stroke volume (SV) and heart rate (HR) were continuously measured, and cardiac output and total peripheral resistance (TPR) were calculated during head-up tilt both before and immediately after the procedure. After phlebotomy, SV was on average reduced by 35 %. With the exception of a short transient fall, MAP was maintained during tilt, both before and after bleeding, despite large variations in SV both within and between the individual experiments. HR and TPR demonstrated considerable compensatory variation. In conclusion, these results show that humans have a remarkable ability to maintain arterial blood pressure during gravitational redistribution of blood, even in cases of severe hypovolemia caused by large acute blood loss.