The amount of cytoplasm within catecholamine neurons occupied by neuromelanin was found to increase progressively with the patient's age. The accretion of neuromelanin was accompanied by an expansion of the cytoplasm of neurons in the substantia nigra and locus ceruleus. These observations support the concept that neuromelanin is a waste product of catecholamine metabolism, derived from the oxidation of dopamine, nonrepinephrine, and related compounds to quinones. The existence of oxidative pathways for catecholamines suggests that defects in their compartmentalization, transport, or degradation may present the cell with sufficient levels of cytotoxic quinones and free radical species to result in the degeneration of neurons observed in Parkinson's disease.