Serial determinations of plasma dihydroxyphenylalanine (dopa) in 16 Parkinson's disease patients receiving levodopa showed a negative correlation between plasma dopa levels and disability scores among patients who exhibited daily fluctuations of signs and symptoms. This suggests that the amount of levodopa delivered to the brain from the periphery is of major importance in the production of the “on-off” phenomenon. A close relationship between plasma dopa levels and abnormal involuntary movements was present in six patients. In three a striking dissociation between control of Parkinson's disease and abnormal involuntary movements was present, suggesting that in some patients these two effects are mediated through different underlying mechanisms. Administration of levodopa in such a way as to prevent both high and low levels of dopa in plasma minimizes disability in Parkinson's disease and may lessen abnormal involuntary movements in patients with the “on-off” effect.