Concentrations of homovanijlic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) were studied before and during treatment of 151 parkinsonian patients with levodopa alone or combined with a decarboxylase inhibitor. A particular attempt was made in this study to determine whether any correlation exists between the concentrations of these acid monoamine metabolites in the CSF before and during treatment as well as after administration of probenecid and the therapeutic response and side-effects of the treatment. In patients with Parkinson’s disease the concentrations of HVA and 5-HIAA in the CSF before therapy and after administration of probenecid were found to be significantly lower than those in control subjects. Statistical analyses showed that these variables could not be used to predict the clinical response to treatment. Long-term treatment with levodopa alone or combined with a decarboxylase inhibitor induced an increase in the concentration of HVA in the CSF which correlated significantly with the dose of the drug but not with the clinical improvement. However, the concentrations of HVA during combined treatment were considerably lower than during treatment with levodopa alone, using therapeutically equivalent dosages. Obviously, a part of the HVA found in the CSF during levodopa treatment originates from the brain capillary walls. Treatment with levodopa and decarboxylase inhibitor decreased the concentration of 5-HIAA in the CSF. During treatment with levodopa alone, there was a significant negative correlation with the dose of levodopa as well as with libido and psychotic behavior after 6 and 12 months’ treatment, respectively.