Comparison of high angular resolution diffusion imaging (HARDI) measurements between subjects or between timepoints for the same subject are facilitated by spatial normalization. In this work an algorithm was developed to transform the fiber orientation distribution (FOD) function, based on HARDI data, taking into account not only translation, but also rotation, scaling, and shearing effects of the spatial transformation. The algorithm was tested using simulated data and intrasubject and intersubject normalization of in vivo human data. All cases demonstrated reliable transformation of the FOD. This technique makes it possible to compare the intravoxel fiber distribution between subjects, between groups, or between timepoints for a single subject, which will be helpful in HARDI studies of white matter disease. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc.