There is currently no general agreement on the enzymatic basis of neuromelanin synthesis. It is generally agreed that neuromelanin synthesis must differ from melanin synthesis in skin, since "tyrosinase" (aerobic dopa oxidase) is not present in brain. Various proposals have suggested that monoamine oxidase, prostaglandin H synthetase, or peroxidase may catalyze neuromelanin formation from dopa, dopamine and norepinephrine. It has also been proposed that neuromelanin synthesis may be based on the pseudoperoxidase activity of metal ions. Our group was the first to demonstrate enzymatic peroxidase activity in brain, which was subsequently confirmed by three other laboratories. Our group was also the first to demonstrate the melanogenic activity of brain peroxidase (subsequently confirmed by another laboratory) and to propose that peroxidase is the key enzyme in neuromelanin synthesis because of this potential and because of its presence in lysosomes, the subcellular site of neuromalin.