Current semiautomated magnetic resonance (MR)-based brain segmentation and volume measurement methods are complex and not sufficiently accurate for certain applications. We have developed a simpler, more accurate automated algorithm for whole-brain segmentation and volume measurement in T 1-weighted, three-dimensional MR images. This histogram-based brain segmentation (HBRS) algorithm is based on histograms and simple morphological operations. The algorithm's three steps are foreground/background thresholding, disconnection of brain from skull, and removal of residue fragments (sinus, cerebrospinal fluid, dura, and marrow). Brain volume was measured by counting the number of brain voxels. Accuracy was determined by applying HBRS to both simulated and real MR data. Comparing the brain volume rendered by HBRS with the volume on which the simulation is based, the average error was 1.38%. By applying HBRS to 20 normal MR data sets downloaded from the Internet Brain Segmentation Repository and comparing them with expert segmented data, the average Jaccard similarity was 0.963 and the κ index was 0.981. The reproducibility of brain volume measurements was assessed by comparing data from two sessions (four total data sets) with human volunteers. Intrasession variability of brain volumes for sessions 1 and 2 was 0.55 ± 0.56 and 0.74 ± 0.56%, respectively; the mean difference between the two sessions was 0.60 ± 0.46%. These results show that the HBRS algorithm is a simple, fast, and accurate method to determine brain volume with high reproducibility. This algorithm may be applied to various research and clinical investigations in which brain segmentation and volume measurement involving MRI data are needed.