Defects of respiratory chain complexes were considered as possible pathogenetic mechanisms in Parkinson's disease (PD). Changes of cytochrome c oxidase (COX) in four different nuclei of the substantia nigra of 8 PD cases and 10 age-matched controls were investigated by means of morphometry and immunohistochemistry. Pigmented neurons with COX defects were randomly distributed within the the four nuclei of PD cases, but only in the posterolateral nucleus was the numerical density of pigmented neurons with COX defects significantly increased compared with controls. The numerical density of pigmented neurons without COX defects was significantly reduced in the anteromedial, anterointermediolateral, and posterolateral nuclei in PD. The cell size of pigmented neurons with and without COX defects was significantly diminished in the anteromedial and posterolateral nuclei of PD cases. It is suggested that complex IV defects in nigral neurons are most probably a result of accelerated aging, but are least likely to be a primary aspect of the pathogenetic processes occurring in PD.