The distribution of calbindin-D28K (CaBP)-positive neurons was investigated by immunohistochemistry in 4 controls, 5 cases of Parkinson's disease and a single case of strionigral degeneration. CaBP-positive neurons were preferentially localized to the mediodorsal portion of the substantia nigra pars compacta (SNC) in the beta layer, while CaBP-negative, melanin-positive neurons were concentrated in the ventrolateral SNC in the alpha layer. In Parkinson's disease and the case of strionigral degeneration, there was a relative sparing of the CaBP-positive neurons compared with CaBP-negative, pigmented neurons. These data imply that CaBP may confer some protection to SNC dopaminergic neurons against the pathological process which is responsible for Parkinson's disease and strionigral degeneration.