In this work, we describe methodologies for serial volumetric measurements of hippocampi and cerebella. Serial scans were co-registered and intensity matched prior to the volumetric measurements. Manual drawing was used to define the boundaries of the hippocampi. For the cerebellar volumetric measurements, the brain was automatically segmented from the co-registered scans; manual drawing was used to define the boundary between the cerebellum and the cerebrum and brainstem. The operator was blinded to the nature of the subject (patient or normal control) and the chronological order of the scans. The coefficient of reliability of hippocampal volume measurements in a group of 20 controls was 0.078 cm(3) (3.1% of the mean baseline volume); for the cerebellum, the value was 3.8 cm(3) (3.0% of the mean baseline volume). We conclude that the methods presented are valid and that the software provides a useful integrated tool for the quantitative analysis of structural changes in serially acquired volume MRI data in prospective, blinded studies.