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In six control subjects pars compacta nerve cells in the ventrolateral substantia nigra had a lower melanin content than nerve cells in the dorsomedial region. This coincides with a natural anatomical division into ventral and dorsal tiers, which represent functionally distinct populations. In six cases of Parkinson's disease (PD) the ventral tier showed very few surviving nerve cells compared with preservation of cells in the dorsal tier. In 13 subjects without PD, but with nigral Lewy bodies and cell loss, the degenerative process started in the ventral tier, and spread to the dorsal tier. This pattern of selective degeneration of nigrostriatal neurons is not seen in ageing or after acute administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).