SUMMARY The acid metabolites of dopamine and 5-hydroxytryptamine were estimated in the lumbar cerebrospinal fluid (CSF) of Parkinsonian patients both before and during treatment with L-dopa,' the amino acid precursor of dopamine. An attempt was made to relate clinical improvement to the biochemical results. The dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, showed increases related to the dose of L-dopa, the increase in homovanillic acid concentration being proportionately greater than that of 3,4-dihydroxyphenylacetic acid. The concentration of the 5-hydroxytryptamine metabolite, 5-hydroxyindol-3-ylacetic acid, was unaltered by the drug. Clinical improvement, which in the early stages was evident particularly in the bradykinesia, was found to occur at doses of L-dopa greater than 1-5 g/day. Effective doses of L-dopa gave rise to concentrations of dopamine metabolites in the CSF which were greater than normal. Possible implications of these findings are discussed.The existence of lower concentrations of dopamine in the caudate nucleus and substantia nigra in Parkinsonian patients than in a control group (Ehringer and Hornykiewicz, 1960; Hornykiewicz, 1962) has led to the suggestion that a change in the metabolism of this amine is associated with the syndrome. This concept is supported by the finding that the main metabolite of dopamine, homovanillic acid, is also present in reduced concentrations in the brain and in the CSF of these patients

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