So far, little attention has been paid to the biomechanical aspects of decompressive craniectomy. The brain tissue deformation occurring in these patients is difficult to quantify. Twenty-six patients suffering from a large bone defect after craniectomy were examined in supine position. The third ventricle's axial diameter was measured by transcranial ultrasound. Subsequently, the patient was brought into a sitting position. After 5 minutes, another measurement was taken. This procedure was repeated about 7 days after cranioplasty. The patients were grouped according to "early cranioplasty" (cranioplasty within 40 days after craniectomy, median 30 days) and "late cranioplasty", (cranioplasty more than 40 days, median 80 days). Data of 13 healthy volunteers were used as a reference standard. In the healthy volunteers, the third ventricle was enlarging after reaching the sitting position. The median diameter was 2.35 mm in the lying and 2.9 mm in the sitting position (p > 0.05). In the patients before early cranioplasty, a decrease of the diameter after reaching the sitting position was observed. The mean diameter was 7.0 mm in the lying and 5.9 mm in the sitting position (p > 0.01). This difference was not significant in patients before late cranioplasty (9.7 vs. 9.4 mm). After cranioplasty, the mean diameter was 6.6 and 6.2 mm in the early cranioplasty group and 9.2 mm and 9.4 mm in the late cranioplasty group (lying and sitting position, respectively). This data demonstrate for the first time that unphysiological orthostatic brain tissue deformation occurs in patients after craniectomy.