Two missense mutations in the gene encoding α-synuclein have been linked to rare, early-onset forms of Parkinson's disease (PD). These forms of PD, as well as the common idiopathic form, are characterized by the presence of cytoplasmic neuronal deposits, called Lewy bodies, in the affected region of the brain. Lewy bodies contain α-synuclein in a form that resembles fibrillar Aβ derived from Alzheimer's disease (AD) amyloid plaques. One of the mutant forms of α-synuclein (A53T) fibrillizes more rapidly in vitro than does the wild-type protein, suggesting that a correlation may exist between the rate of in vitro fibrillization and/or oligomerization and the progression of PD, analogous to the relationship between Aβ fibrillization in vitro and familial AD. In this paper, fibrils generated in vitro from α-synuclein, wild-type and both mutant forms, are shown to possess very similar features that are characteristic of amyloid fibrils, including a wound and predominantly unbranched morphology (demonstrated by atomic force and electron microscopies), distinctive dye-binding properties (Congo red and thioflavin T), and antiparallel β-sheet structure (Fourier transform infrared spectroscopy and circular dichroism spectroscopy). α-Synuclein fibrils are relatively resistant to proteolysis, a property shared by fibrillar Aβ and the disease-associated fibrillar form of the prion protein. These data suggest that PD, like AD, is a brain amyloid disease that, unlike AD, is characterized by cytoplasmic amyloid (Lewy bodies). In addition to amyloid fibrils, a small oligomeric form of α-synuclein, which may be analogous to the Aβ protofibril, was observed prior to the appearance of fibrils. This species or a related one, rather than the fibril itself, may be responsible for neuronal death.