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We investigated the registration of ultrasound volumes based on the mutual information measure, a technique originally applied to multimodality registration of brain images. A prerequisite for successful registration is a smooth, quasi-convex mutual information surface with an unambiguous maximum. We discuss the necessary preprocessing to create such a surface for ultrasound volumes. Abdominal and thoracic organs imaged with ultrasound typically move relative to the exterior of the body and are deformable. Consequently, four specific instances of image registration involving progressively generalized transformations were studied: rigid-body, rigid-body + uniform scaling, rigid-body + nonuniform scaling, and affine. Registration was applied to clinically acquired volumetric images. The accuracy was comparable with the voxel dimension for all transformation modes, although it degraded as the transformation grew more complex. Likewise, the capture range became narrower with the complexity of transformation. As the use of real-time three-dimensional ultrasound becomes more prevalent, the method we present should work well for a variety of applications examining serial anatomic and physiologic changes. Developers of these clinical applications would match the deformation model of their problem to one of the four transformation models presented here.