We propose the boundary shift integral (BSI) as a measure of cerebral volume changes derived from registered repeat three-dimensional (3-D) magnetic resonance (MR) [3D MR] scans. The BSI determines the total volume through which the boundaries of a given cerebral structure have moved and, hence, the volume change, directly from voxel intensities. We found brain and ventricular BSI's correlated tightly (r = 1.000 and r = 0.999) with simulated volumes of change. Applied to 21 control scan pairs and 11 scan pairs from Alzheimer's disease (AD) patients (mean interval 386 days) the BSI yielded mean brain volume loss of 1.8 cc (controls) and 34.7 cc (AD); the control group was tightly bunched (SD = 3.8 cc) and there was wide group separation, the group means differing by 8.7 control group standard deviations (SD's). A measure based on the same segmentation used by the BSI yielded similar group means, but wide spread in the control group (SD = 13.4 cc) and group overlap, the group means differing by 2.8 control group SD's. The BSI yielded mean ventricular volume losses of 0.4 cc (controls) and 10.1 cc (AD). Good linear correlation (r = 0.997) was obtained between the ventricular BSI and the difference in their segmented volumes. We conclude the BSI is an accurate and robust measure of regional and global cerebral volume changes.