This study aims to investigate the possibility of generating stereological estimations of total intracranial volume (TIV) on CT scans. The study group included 16 consecutive patients referred for a cranial CT examination. The TIV was estimated using the stereological point counting technique. Volume measurements were optimized by systematically sampling CT sections and by defining an optimum spacing between test points of the grid. The intraobserver and interobserver variability of the optimized volumetric technique was determined. Stereological TIV estimations were compared with the respective planimetric measurements. The application of a test grid with a point spacing of 2.4 cm on 6-8 systematically sampled CT sections provided TIV estimations with a coefficient of error of less than 5%. The intraobserver and interobserver coefficient of variation values were found to be 2.4 and 4.0%, respectively. The 95% limits of agreement between stereological and planimetric TIV measurements were equal to -91.4 and 103.4 cm3. The mean time (±SD) needed to obtain stereological TIV estimations was 2.9±0.6 min. The application of the optimized stereological technique on CT scans enables the efficient estimation of TIV.