This paper describes the development and use of a brain tissue probability model for the segmentation of multiple sclerosis lesions in magnetic resonance (MR) images of the human brain. Based on MR data obtained from a group of healthy volunteers, the model was constructed to provide prior probabilities of grey matter, white matter, ventricular cerebrospinal fluid (CSF), and external CSF distribution per unit voxel in a standardized 3- dimensional `brain space.' In comparison to purely data-driven segmentation, the use of the model to guide the segmentation of multiple sclerosis lesions reduced the volume of false positive lesions by 50%.