We monitored the motor response and plasma and ventricular CSF (CSFv) concentrations of L-dopa during IV infusions of L-dopa in two patients with advanced Parkinson's disease. Concentrations of L-dopa in CSFv mirrored, but lagged behind, those in plasma. In the fasting state, the duration, but not the magnitude, of the motor response was greater with increasing plasma and CSFv levels of L-dopa. During IV infusions of L-dopa following oral administration of phenylalanine, a large neutral amino acid that shares a transport system into the brain with L-dopa, the duration of the motor response was markedly attenuated despite undiminished CSFv levels of L-dopa. These observations suggest that either L-dopa entry into CSFv and the brain are differentially affected by phenylalanine or that phenylalanine affects other steps in the motor response. These observations demonstrate that, except in the fasting state, L-dopa in CSFv is not a reliable predictor of motor response.