Parkinson's disease is a widespread degenerative illness affecting the human central, peripheral, and enteric nervous systems. The underlying pathological process progresses slowly but relentlessly and involves multiple neuronal systems. The disease is the consequence of changes in the neuronal cytoskeleton developing in only a few susceptible types of nerve cells. Afflicted neurons eventually produce Lewy bodies in their perikarya and Lewy neurites in their neuronal processes. Immunoreactions against the presynaptic protein alpha-synuclein have revealed many kinds of inclusion bodies ranging from inconspicuous dot- or thread-like forms to particularly voluminous types. The selective vulnerability of nerve cells induces a distinctive distribution pattern of lesions which remains remarkably consistent across cases. Components of the limbic system and the motor system have been shown to be particularly vulnerable to severe destruction. Some subnuclei of the substantia nigra also undergo major changes. This damage is consistently accompanied by extranigral alterations, with predilection sites including the entorhinal region, the second sector of the Ammon's horn, and important subnuclei of the amygdala. In addition, the nucleus of the stria terminalis, components of the hypothalamus, all of the non-thalamic nuclei with diffuse projections to the cerebral cortex, and most of the centers regulating autonomic functions exhibit severe lesions.