In the brains of humans and other mammals, there are two principal groups of cholinergic nuclei aside from those forming the cranial motor nuclei. One group lies in the forebrain and includes the nucleus basalis of Meynert. The second group lies in the hindbrain and includes the nucleus tegmenti pedunculopontinus (NPP), identified by Mesulam et al. [Mesulam, M.-M., Mufson, E. J., Wainer, B. H. & Levey, A. I. (1983) Neuroscience 10, 1185-1201] as cholinergic cell group Ch5. The basal forebrain cholinergic cell groups, which innervate widespread areas of the neocortex, undergo degeneration in Alzheimer disease and also in parkinsonism associated with dementia. We here report that the hindbrain NPP Ch5 cell group, thought to innervate many nuclei of the extrapyramidal motor system, the superior colliculus, and the substantia innominata, undergoes degeneration in idiopathic Parkinson disease and in the parkinsonian syndrome of progressive supranuclear palsy. These findings strongly suggest that degeneration in the brainstem in Parkinson disease is not confined to catecholamine-containing neurons, but that cholinergic neurons of the NPP are also vulnerable. The findings further raise the possibility that certain symptoms of Parkinson disease and progressive supranuclear palsy have their genesis in pathology of these cholinergic neurons.