We investigated clinical features of adverse reactions to long-term levodopa therapy by the multivariate analysis. Dyskinesia, wearing off effect, on-off effect, mental symptoms, and frozen gait were noted in 29 (11.2%), 78 (30.0%), 17 (6.5%), 45 (17.7%), and 52 (20.0%), respectively, of 260 patients with Parkinson's disease to whom levodopa had been administered for over one year. In the statistical investigation by the multivariate analysis (quantification method type II), the age of initial levodopa therapy, the duration from the onset to the initiation of levodopa therapy, and the duration of levodopa therapy were not closely related to the development of any adverse reaction, while Hoehn & Yahr's stage and the dosage of levodopa had the most significant influence on the development of adverse reactions. Furthermore, concomitant use of amantadine hydrochloride produced an inhibitory effect on the development of dyskinesia. We conclude that early institution of levodopa therapy in Parkinson's disease may not be an important risk factor of adverse reactions.