Neuronal subpopulations of the substantia nigra pars compacta can be separated into two functionally distinct nigrostriatal projections, the ventral tier which is poorly melanised, and the dorsal tier which is well melanised. In Parkinson's disease, juvenile-onset parkinsonism with dystonia and striatonigral degeneration the ventral tier is more vulnerable than the dorsal tier. The ventral tier mostly projects to the putamen, which is vulnerable in striatonigral degeneration and Huntington's disease. In Huntington's disease spiny neurons of the striatal matrix and neurons of the pars reticulata are particularly susceptible. Determining patterns of selective neuronal death may lead to identification of pathogenetic mechanisms.