An average CT brain image is constructed to serve as reference frame for inter-subject registration. A set of 96 clinical CT images is used. Registration includes translation, rotation, and anisotropic scaling. A temporary average based on a subset of 32 images is constructed. This image is used as reference for the iterative construction of the average CT image. This approach is computationally efficient and results in a consistent registration of the 96 images. Registration of new images to the average CT is more consistent than registration to a single CT image. The use of the average CT image is illustrated. © 2003 Elsevier Ltd. All rights reserved.