The contribution of acute physical exercise to the motor fluctuations occurring in advanced Parkinson's disease was studied in four patients using a standard treadmill protocol. With a constant optimal-dose intravenous levodopa infusion, no changes in plasma drug levels or antiparkinsonian response were observed during or for 60 min following a 35-min exercise period, during which the work load increased from minimal to vigorous. Although an effect of exercise on levodopa absorption from the gastrointestinal tract cannot be excluded, there seems to be no basis on which to implicate acute physical activity, at levels ordinarily experienced by parkinsonian patients, in the pathogenesis of the fluctuations in motor performance.