MNI coordinates determined using SPM2 and FSL/FLIRT with the ICBM-152 template were compared to Talairach coordinates determined using a landmark-based Talairach registration method (TAL). Analysis revealed a clear-cut bias in reference frames (origin, orientation) and scaling (brain size). Accordingly, ICBM-152 fitted brains were consistently larger, oriented more nose down, and translated slightly down relative to TAL fitted brains. Whole brain analysis of MNI/Talairach coordinate disparity revealed an ellipsoidal pattern with disparity ranging from zero at a point deep within the left hemisphere to greater than 1-cm for some anterior brain areas. MNI/Talairach coordinate disparity was generally less for brains fitted using FSL. The mni2tal transform generally reduced MNI/Talairach coordinate disparity for inferior brain areas but increased disparity for anterior, posterior, and superior areas. Coordinate disparity patterns differed for brain templates (MNI-305, ICBM-152) using the same fitting method (FSL/FLIRT) and for different fitting methods (SPM2, FSL/FLIRT) using the same template (ICBM-152). An MNI-to-Talairach (MTT) transform to correct for bias between MNI and Talairach coordinates was formulated using a best-fit analysis in one hundred high-resolution 3-D MR brain images. MTT transforms optimized for SPM2 and FSL were shown to reduced group mean MNI/Talairach coordinate disparity from a 5-13 mm to 1-2 mm for both deep and superficial brain sites. MTT transforms provide a validated means to convert MNI coordinates to Talairach compatible coordinates for studies using either SPM2 or FSL/FLIRT with the ICBM-152 template. Hum Brain Mapp 2007. © 2007 Wiley-Liss, Inc.