Abstract: This paper presents a new 3-D image registration method based on the Hotelling transform. Compared with intensity based registration methods using the whole volume intensity information, our approach utilizes Hotelling transform to align images. We evaluate the effectiveness of this approach by applying it to the simulated and real brain image data (MR, CT, PET, and SPECT). The experimental results indicate that the algorithm is effective, especially for 3-D medical images.