A data analysis method was developed for neuronal activation studies using [15O]water positron emission tomography (PET). The method consists of several procedures including intra-subject head motion correction (co-registration), detection of the mid-sagittal plane of the brain, detection of the intercommissural (AC-PC) line, linear scaling and non-linear warping for anatomical standardization, pixel-by-piexl statistical analysis, and data display. All steps are performed in three dimensions and are fully automated. Each step was validated using a brain phantom, computer simulations, and data from human subjects, demonstrating accuracy and reliability of the procedure. The method was applied to human neuronal activation studies using vibratory and visual stimulations. The method detected significant blood flow increases in the primary sensory cortices as well as in other regions such as the secondary sensory cortex and cerebellum. The proposed method should enhance application of PET neuronal activation studies to the investigation of higher-order human brain functions.