Motor fluctuations and dyskinesias in Parkinsonian patients may be at least partially due to fluctuations of levodopa plasma concentrations. Sustained-release (SR) formulations of levodopa may present a promising, effective solution of this problem. Therefore we performed a 4-fold, cross-over double-blind trial with a new SR preparation, tested in healthy volunteers (Gerlach et al., 1988) before, in 12 Parkinsonian subjects. Two different dosages of the pure new levodopa SR-preparation, a composition of 70% SR and 30% levodopa immediate release (IR) and a conventional IR levodopa preparation were compared by their pharmacokinetic behaviour and their clinical effects. The relative bioavailability of levodopa in plasma was 69% for the combination of SR and IR levodopa release, for the pure SR formulations (100 mg levodopa) 54% and (200 mg levodopa) 55%, compared to the 100% of the standard form of IR release of 100 mg levodopa. In contrast to the conventional IR formulation the pharmacokinetic behaviour of the SR preparations showed no initial sharp peak, but more continuous and longer maintaining plasma concentrations of levodopa. Due to the small numbers of cases and the missing homogenity of the selected patients no statistical significant differences between the four preparations regarding the clinical response were observed. But the described pharmacokinetic behaviour gives hope, that these newly developed SR-preparations may lead to progress in the treatment of Parkinson's disease (prolongation of dosage intervals, reduction of motor fluctuations).