Two patients with varicella-zoster virus leukoencephalitis and acquired immunodeficiency syndrome are described. Neither patient had cutaneous or disseminated varicella-zoster virus infection within the last six months of life. Demyelinated lesions resembling those of progressive multifocal leukoencephalopathy were seen in their brains at autopsy. Numerous cells with Cowdry type A intranuclear inclusions surrounded the lesions; these cells stained positively for varicella-zoster virus with immunohistochemistry and contained herpesvirus nucleocapsids by electron microscopy. Leptomeningeal vessels accompanying the lesions displayed a zoster-induced vasculopathy in one of the two patients. Vascular and parenchymal central nervous system infections with varicella-zoster virus are rare in the absence of cutaneous lesions, and to our knowledge, the presence of both in one patient has not yet been described.