Five patients with a demyelinating disorder and associated amyloid angiopathy are presented. The disease affected middle-aged individuals, pursued a fluctuating course, and ended in progressive, fatal deterioration of the central nervous system. Neurologic findings indicated multiple lesions within the neuraxis; profound dementia was prominent in all cases. Pathologically, numerous demyelinated plaques, similar to those in multiple sclerosis, were found in the cerebral white matter, and less consistently in other locations such as optic nerve, brain stem, and spinal cord. Amyloid accumulated massively in and around blood vessels, usually in the immediate vicinity of the plaques. At least one similar case is reported in the literature, but the nosologic status of the condition is uncertain.