A system and method for autofusion of three-dimensional ('3-D') image data volumes is described. According to the system and method, registration is effected by simultaneously displaying on a GUI at least, but preferably, two 3-D, image data volumes, and one of the 3-D image data volumes is held fixed while the other may be scaled, rotated, and translated to align homologous anatomic features. The system and method will simultaneously display the axial, sagittal, and coronal plane views of a region of a region of interest. These plane views will be of data volumes that are designed and configured for a system user to 'drag' or 'position' one volume to a new position in one plane view which will also simultaneously update the data volume in the other two plane views with no apparent lag time. The system and method also includes automated alignment computation based on mutual information (MI) maximization. The system and method aligns 3-D more efficiently and faster than prior image alignment methods.