Five clinically affected and nine at-risk members of a kindred with an autosomal dominant adult-onset leukodystrophy simulating chronic progressive multiple sclerosis were studied with computed tomography (CT) and magnetic resonance imaging (MRI). Computed tomographic scans showed white matter lucencies occurring earliest and most prominently in the frontoparietal region. The lesions were nondiscrete, diffuse, and bilaterally symmetric. These changes were more clearly visualized as areas of increased signal intensity with T2-weighted MRI. Magnetic resonance imaging also showed increased signal intensity in the brain stem, cerebellar white matter, or both of four patients. Both MRI and CT differentiated this entity from multiple sclerosis, but MRI was superior to CT in detailing the extent of white matter involvement.