We have examined by immunohistochemistry the parvalbumin-containing neurons of the substantia nigra in patients with Parkinson's disease and in age-matched controls. Parvalbumin, a calcium binding protein, is involved in buffering intracellular calcium and in this study was localized within the majority of non-pigmented neurons of the human pars reticulata. Previous studies have shown that the parvalbumin-immunoreactive pars reticulata neurons are GABAergic and project to the motor thalamus and tectum. Their increased output, due to the loss of dopaminergic inhibition in Parkinson's disease, decreases cortical activation via thalamic pathways, causing parkinsonian symptoms. In Parkinson's disease there was a significant loss of parvalbumin-immunoreactivity from these neurons, though there was no evidence of actual cell loss. This loss of parvalbumin-immunoreactivity was detected only in those cases with end-stage Parkinson's disease.