Three-dimensional intra- and intersubject registration of image volumes is important for tasks that include quantification of temporal/longitudinal changes, atlas-based segmentation, computing population averages, or voxel and tensor-based morphometry. While a number of methods have been proposed to address this problem, few have focused on the problem of registering whole body image volumes acquired either from humans or small animals. These image volumes typically contain a large number of articulated structures, which makes registration more difficult than the registration of head images, to which the majority of registration algorithms have been applied. This article presents a new method for the automatic registration of whole body computed tomography (CT) volumes, which consists of two main steps. Skeletons are first brought into approximate correspondence with a robust point-based method. Transformations so obtained are refined with an intensity-based nonrigid registration algorithm that includes spatial adaptation of the transformation's stiffness. The approach has been applied to whole body CT images of mice, to CT images of the human upper torso, and to human head and neck CT images. To validate the authors method on soft tissue structures, which are difficult to see in CT images, the authors use coregistered magnetic resonance images. They demonstrate that the approach they propose can successfully register image volumes even when these volumes are very different in size and shape or if they have been acquired with the subjects in different positions.