Double-blind and non-blind therapeutic trials of orally administered L-Dopa in the long-term treatment of Parkinsonism were carried out with 126 patients. For correlative studies the amount of hornovanillic acid (HVA) in the cerebrospinal fluid (CSF) was analysed. A double-blind cross-over trial with 1.5 g of L-Dopa for 2 months was performed in 10 patients. During L-Dopa treatment 8 patients showed improvement but only 2 patients benefited with placebo. In a double-blind study 40 patients were treated with a daily dosage of 5 g of L-Dopa for 2 months. All patients showed benefit on L-Dopa during this trial period and L-Dopa induced highly significantly more improvement than placebo. During non-blind treatment with optimal dosage of L-Dopa followed up for 1 to 9 months, all but one of 76 parkinsonian patients showed overall improvement. The average dose needed for optimal improvement was usually between 4 and 5 g daily. 41 % of the patients were markedly or very markedly improved and 48 °/o moderately improved; only 11 % showed minimal benefit or none. All the cardinal symptoms of Parkinson’s disease were significantly alleviated. Patients with severe disease and with duration of disease of 15 years or more showed less marked improvement. In some patients changing of anticholinergic drug therapy during L-Dopa treatment indicated a synergistic effect. Nausea, vomiting, anorexia, postural hypotension and involuntary movements were the most frequent clinical side effects. L-Dopa treatment had to be discontinued in 2 patients after 2 months treatment because of mental disturbances. An increase in libido was reported by 25 % of the patients and 5 postmenopausal female patients had renewed menstrual bleeding. During L-Dopa treatment the amount of HVA in the CSF rose significantly in all patients and was correlated with the dose of L-Dopa but not clearly with the clinical improvement. The results indicated the significant value of high oral doses of L-Dopa in the long-term treatment of parkinsonian patients. It is concluded that the therapeutic response to L-Dopa is associated with an increase in brain dopamine metabolism but that there is not always a direct correlation.