A 47-year-old man with acquired immunodeficiency syndrome presented 3 months antemortem with the onset of lower extremity sensory abnormalities. A progressive course of multifocal weakness and sensory disturbances ensued. Electrophysiologic studies revealed a generalized asymmetric demyelinating polyneuropathy with secondary axonal loss. The patient was sequentially treated with plasmapheresis, high dose corticosteroids, intravenous immune globulin, and ganciclovir. His neuropathy progressed, and he died of a fulminant bronchopneumonia. At autopsy the patient had a multifocal cytomegalovirus polyradiculoneuropathy, with both demyelinative and necrotizing features. While cytomegalovirus may be associated with a variety of peripheral nerve syndromes, its clinical presentation as a primary demyelinating polyneuropathy is unusual. Its importance vis-à-vis potential therapy for AIDS-associated neuropathies is discussed.