Treatment of Parkinson’s disease with amantadine and L-dopa was studied in 82 patients. A double-blind cross-over trial with 38 patients showed a significant benefit with 200 mg of amantadine daily. During non-blind treatment with 300 mg of amantadine for 2–4 months 60% of the patients showed moderate or marked overall improvement. The results were independent of age, sex, duration or severity of the disease or previous thalamotomy. During combined treatment an additive effect of L-dopa, but not that of amantadine, was demonstrated showing that the therapeutic effect of L-dopa is superior to that of amantadine. Furthermore, an increased number of clinical side-effects, especially nausea and vomiting were found during combined treatment. Moreover, the response to L-dopa could not be predicted with amantadine. Amantadine treatment did not induce changes in the concentration of HVA and 5-HIAA in the CSF although there is a strong evidence of a monoamine-releasing effect of amantadine on experimental animals.