Responses in plasma concentration of levodopa to administration of levodopa alone or combined with the extracerebral decarboxylase inhibitor, Ro 4-4602, were studied in 173 parkinsonian patients both after single and sequential administration. It was also determined whether any correlation existed between plasma levodopa and clinical responses to treatment. Maximum plasma levels of levodopa were reached in 1–2 h after a single oral administration and correlated with the dose. Sustained-release and standard levodopa preparations induced similar half-lives of levodopa in the plasma but there was a significantly lower mean concentration at 30 min after administration of sustained release levodopa. 200 or 150 mg of levodopa combined with 50 or 100 mg of decarboxylase inhibitor, respectively, resulted in plasma levels of levodopa equal to those achieved with 1,000 mg of levodopa alone. A sequential dose of these levodopa preparations every 4 h resulted in repeated peak concentrations of plasma levodopa 2 h after administration followed by low values at 4 h. Correlation analyses showed that clinical improvement during long-term treatment with optimal dosage was not related to the concentration of circulating levodopa in the plasma. However, plasma levodopa correlated significantly with some of the clinical side-effects, especially with vomiting and involuntary movements. To avoid too high peak concentrations of plasma levodopa and consequently too numerous side-effects, it would be better to give the daily dosage of levodopa in many relatively low doses than in a few large ones.