Purpose: Automatic brain-lesion segmentation has the potential to greatly expand the analysis of the relationships between brain function and lesion locations in large-scale epidemiologic studies, such as the ACCORD-MIND study. In this manuscript we describe the design and evaluation of a Bayesian lesion-segmentation method, with the expectation that our approach would segment white-matter brain lesions in MR images without user intervention. Materials and Methods: Each ACCORD-MIND subject has T1-weighted, T2-weighted, spin-density-weighted, and FLAIR sequences. The training portion of our algorithm first registers training images to a standard coordinate space; then, it collects statistics that capture signal-intensity information, and residual spatial variability of normal structures and lesions. The classification portion of our algorithm then uses these statistics to segment lesions in images from new subjects, without the need for user intervention. We evaluated this algorithm using 42 subjects with primarily white-matter lesions from the ACCORD-MIND project. Results: Our experiments demonstrated high classification accuracy, using an expert neuroradiologist as a standard. Conclusions: A Bayesian lesion-segmentation algorithm that collects multi-channel signal-intensity and spatial information from MR images of the brain shows potential for accurately segmenting brain lesions in images obtained from subjects not used in training.