Serial 3D MR scan pairs (1 year intervals) from nine control subjects and nine Alzheimer disease (AD) patients were matched using an accurate fast fluid algorithm. Subtraction of matched scans indicated near complete cancellation of brain structure; mean cross-correlation coefficients were 0.946 (controls) and 0.933 (AD). In the AD group, regions of expansion and contraction in the deformation field were consistent with the known patterns of tissue loss and expansion of CSF spaces. Fluid registration may permit better localization of structural change.