We evaluated postural effects on intracranial pressure (ICP) and cerebral perfusion pressure (CPP: mean arterial pressure (MAP) - ICP) in neurosurgical patients undergoing 24-hour ICP monitoring as part of their diagnostic workup. We identified 9 patients (5 women, age 44±20 yrs.; mean±SD) who were "as normal as possible" i.e. without indication for neurosurgical intervention (e.g. focal lesions, global edema, abnormalities in ICP-profile or cerebrospinal fluid dynamics). ICP (tip-transducer probe, Raumedic) in the brain parenchyma (N=7) or in the lateral ventricles (N=2) and cardiovascular variables (Nexfin) were determined from 20° head-down tilt to standing up. Compared to the supine position, ICP increased during 10° and 20° of head-down tilt (from 9.4±3.8 to 14.3±4.7 and 19±4.7 mmHg, P<0.001). Conversely, 10° and 20° head-up tilt reduced ICP to 4.8±3.6 and 1.3±3.6 mmHg and ICP reached -2.4±4.2 mmHg when standing up (P<0.05). Concordant changes in MAP maintained CPP at 77±7 mmHg regardless of body position (P=0.95). During head-down tilt, the increase in ICP corresponded to a hydrostatic pressure gradient with reference just below the heart, likely reflecting the venous hydrostatic indifference point. When upright, the decrease in ICP was attenuated, corresponding to formation of a separate hydrostatic gradient with reference to the base of the skull, likely reflecting the site of venous collapse. ICP therefore seems to be governed by pressure in the draining veins and collapse of neck veins may protect the brain from being exposed to a large negative pressure when upright. Despite positional changes in ICP, MAP keeps CPP tightly regulated.