We report a magnetic resonance imaging (MRI) study in a large number of subjects that examines various analytic techniques for anatomical landmark information. The initial issue involved interrater reliability in locating landmarks along the midsagittal plane. Another issue dealt with using landmarks to register (linear) individual scans for subsequent analyses or more sophisticated registration techniques. We next explore the use of interlandmark distances as indices of brain size. Twenty-seven landmarks were chosen from the midsagittal slice of 101 abnormal subjects. Interrater reliability estimates on a subset of the scans were excellent overall. Rotating to anterior-posterior commissure points was the best of the tested two-point registrations, although an average angular rotation was better. Reliability and validity for landmark-derived measures of size were excellent. Landmark-based analyses offer opportunities to explore shape and size questions, although they are not appropriate for addressing all questions. Under specific conditions, landmark data can be generated quickly and accurately.