Immunohistochemical localization of the Ca(2+)-binding protein parvalbumin (PV) was investigated in the adult human central nervous system (CNS). The antiserum against purified rat skeletal muscle PV specifically recognized certain neuronal populations and their processes. Strongly positive were Purkinje, basket and stellate cells of the cerebellum, cerebral cortical nonpyramidal cells, and neurons in the thalamic reticular and ventrolateral nuclei, subthalamic nucleus, lateral and medial geniculate bodies, vestibular and cochlear nuclei, spinal trigeminal nucleus, cuneate and gracile nuclei, and dorsal nucleus of Clarke. Negative were cortical pyramidal neurons, neurons of the autonomic nerves, and neurons in the caudate nucleus, putamen, dentate nucleus, inferior olive, and substantia gelatinosa. The number and size of PV-immunoreactive neurons were significantly decreased in Alzheimer's disease. However, the decrease was not disease specific.