An immunohistochemical study was carried out to investigate the topographic distribution of calbindin-D,,k in the human basal ganglia and substantia nigra and its alterations in patients with idiopathic Parkinson's disease (PD), parkinsonism-dementia complex on Guam, progressive supranuclear palsy, and striatonigral degeneration. In normal control subjects, cdbindin-D,,, immunoreactivity was identified in the medium-sized neurons and neuropil of the matrix compartment of the striatum, the woolly fiber arrangements of the globus pallidus, and the fiber structures of the pars reticulata of the substantia nigra. Cdbindin-D,,k expression in the basal ganglia of patients with PD and parkinsonism-dementia on Guam was not different from that of control subjects, suggesting that the matrical output pathway is spared in these disorders. In contrast, its disruption is inferred from the observed disorganization of woolly fibers in the globus pallidus of patients with progressive supranuclear palsy and the reduced ~dbindin-D,,~ reactivity in the putaminal matrix and the pars reticdata of the substantia nigra of subjects with striatal degeneration. Thus, our results indicate that ~albindin-D,,~ is a useful marker for the projection system from the matrix compartment and that its expression is modified in patients with progressive supranuclear palsy and striatal degeneration.