High plasma levels of 3–0-methyldopa (OMD) were found in parkinsonian patients chronically treated with levodopa, particularly in those with on-off phenomenon. However, no relation could be established between circulating levels of the levodopa metabolite and the presence of motor response fluctuations at any stage of disease. It appears unlikely that plasma OMD accumulation contributes to the pathogenesis of wearing-off or on-off responses.