On the basis of the results of a large number of studies of the correlation between plasma levodopa levels and the occurrence of mobility disorders, it was concluded that side-effects such as dyskinesia, end-of-dose, peak-dose and on-off phenomena, which occur especially during levodopa long-term treatment of Parkinson patients, may be caused by fluctuations in the plasma levodopa levels. Some preliminary trials using sustained-release formulations were not up to expectations. Still, we studied the question of whether it might not be possible after all to obtain sustained plasma levodopa levels over prolonged periods of time with levodopa sustained-release (S. R.) formulations, without causing a high initial peak. For this purpose, we compared the pharmacokinetics of six different levodopa S. R. formulations with a standard preparation in two randomized cross-over trials in healthy male volunteers. Although the levodopa S. R. formulations prolonged the time to peak blood levels in all cases, a plateau that was constant over a longer period of time could not be obtained. However, none of the S. R. preparations studied gave rise to a high initial peak of the plasma levodopa concentration. The levodopa concentrations had again returned to endogenous levels within no more than 8 hours of administration of all six levodopa S. R. formulations.