Plasma concentrations 01 dopa were measured during “on” (mobile and dyskinetic) and “off” (akinetic and/or tremulous) episodes in 10 patients who had been treated chronically with levodopa for Parkinson's disease. Dopa levels were higher during “on” than “off” spells (1.29 ± 1.08 versus 0.62 ± 0.59 mcg per milliliter; p < 0.01). A diet containing less than 10 gm per day of protein resulted in higher plasma dopa levels (2.05 ± 1.00 versus 1.20 ± 0.92 mcg per milliliter; p <0.001). The “on-off” effect was greatly relieved by low protein diets in 3 of 1 1 patients, possibly because of decreased competition for absorption by dietary amino acids. These results suggest that extracerebral metabolism of levodopa may be important in the “on-off” effect.