This paper presents a new 3-D image registration method based on the principal component analysis (PCA). Compared with intensity-based registration methods using the whole volume intensity information, our approach utilizes PCA to estimate the centroid and principal axis, and completes the registration by aligning the centroid and principal axis. We evaluated the effectiveness of this approach by applying it to simulated and actual brain image data (MR, CT, PET, and SPECT). The experimental results indicate that the algorithm is effective, especially for registration of 3-D medical images.