The effects of ceruloplasmin, a blu copper-containing serum glycoprotein, on the oxidation of the neurotoxin 6-hydroxydopamine in several chemical environments were studied. The spontaneous autoxidation of 6-hydroxydopamine proceeded by a free radical chain reaction involving O-2(-.) and produced the corresponding chromogen 6-hydroxydopaminequinone and hydrogen peroxide. The process was accelerated in the presence of horse plasma ceruloplasmin. Yields of hydrogen peroxide in the presence of ceruloplasmin were significantly less than those measured in its absence. This is the first evidence of oxidase activity of ceruloplasmin toward a natural substrate, the 6-hydroxydopamine.