Previous pharmacokinetic trials with standard levodopa formulations showed a different behavior of levodopa degradation in plasma of patients with Parkinson's disease (PD) in various advanced stages. The objective of this trial was to compare levodopa plasma metabolism in PD patients with and without previous long-term levodopa intake after oral intake of a dispensable levodopa/benserazide formulation (DLB). The over a 150 min interval computed area under the curve values of levodopa plasma levels after DLB administration were significantly (ANCOVA: F(1,19) = 7.88, P = 0.01) higher in PD patients with chronic levodopa treatment compared to patients without prior levodopa treatment. The maximum plasma levodopa concentration did not differ (ANCOVA: F(1.19) = 1.17, P = 0.29). Long-term levodopa administration results in an increased levodopa plasma bioavailability in PD patients.