In Parkinson's disease (PD), response fluctuations may be due, in part, to pharmacokinetic problems including poor solubility of levodopa and difficulties in its absorption. We administered levodopa ethylester (LDEE), a new highly soluble prodrug of levodopa, by subcutaneous and intramuscular injections to PD patients with response fluctuations, in an open trial to examine its safety and efficacy. Various doses of LDEE (150-400 mg) turned patients 'on' with a high success rate (43 of 45 injections). Latencies to 'turning on' decreased and duration of on responses increased in a dose- dependent manner. LDEE, given either subcutaneously or intramuscularly, produced similar beneficial effects and induced rapid and sustained elevations in plasma levodopa levels. The drug was well tolerated with only minor and negligible side effects. Study suggests that subcutaneous and intramuscular administration of LDEE may be advantageous as a novel therapeutic strategy for response fluctuations. It may be particularly useful to rapidly and predictably rescue patients from a variety of disabling 'off' situations.