Effects of the long term, continuous administration of a dopamine agonist on motor response complications attending levodopa therapy were studied in 7 patients with advanced Parkinson's disease under controlled conditions. After a 3-month round-the-clock infusion of lisuride, the duration of antiparkinsonian action of levodopa increased by approximately 90%, and the therapeutic window for the acutely administered dopamine precursor widened by > 300%. These benefits were more than three times greater than those produced by 9 days of continuous levodopa administration. In contrast to the effects on levodopa pharmacodynamics, the continuous infusion of lisuride did not prolong its action, suggesting a lisuride effect on presynaptic as well as postsynaptic dopaminergic mechanisms. These results lend further support to the view that continuous dopamine replacement ameliorates motor fluctuations and peak-dose dyskinesias that complicate standard levodopa regimens. Our findings further suggest that alterations at both presynaptic and postsynaptic levels contributing to these motor complications tend to normalize with the more physiological stimulation afforded by continuous replacement strategies, especially when given chronically.