We describe five patients with a chronic asymmetric sensorimotor neuropathy most pronounced in the upper extremities with focal involvement of individual nerves. Diagnosis was established by electrophysiologic evidence of persistent multifocal conduction block. Sural nerve biopsy in three patients showed primarily demyelinating-remyelinating changes with varying degrees of fiber loss. Two patients had acute optic neuritis, indicating that the disorder was not always restricted to the peripheral nervous system. Two patients treated with corticosteroids improved, whereas three untreated patients had static deficits or steady progression of symptoms. Chronic multifocal demyelinating neuropathy with persistent conduction block seems to be a variant of chronic acquired demyelinating polyneuropathy and may be immunologically mediated.