Axial and sagittal magnetic resonance (MR) sections and contiguous sections of axial positron emission tomographic (PET) images obtained with fludeoxyglucose F-18 were used to evaluate a new method of registering three-dimensional images of the brain. The users specified the interhemispheric fissure plane in three dimensions for both the MR and PET data sets by specifying its endpoints within several axial sections. A transformation matrix aligning the interhemispheric fissure plane in MR and PET space was calculated and used to create one resectioned PET image on the resectioned PET image, and the user specified the remaining translations and rotation by moving the overlaid outline of the MR image. MR and PET data sets in four subjects were registered. The three-dimensional error on average was less than 3.8 mm and never exceeded 7.5 mm. Less than 1 hour per patient was required for registration. The method is accurate unless the interhemispheric fissure deviates significantly from a planar configuration. It does not need thin or contiguous MR sections and provides an estimate of the total registration error for every case.