It has been clarified that long-term levodopa therapy in Parkinson's disease may pose various serious problems of adverse reactions, such as dyskinesia, wearing-off effect, on-off effect, mental symptoms, and frozen gait. At our department, dyskinesia, wearing-off effect, on-off effect, mental symptoms and frozen gait were respectively noted in 29 (11.2%), 78(30.0%), 17(6.5%), 42(16.2%), and 51(19.6%) of 260 patients with Parkinson's disease who had been administered levodopa for over one year. In the statistical investigation by the multiple analysis, the time from first onset to initiation on levodopa therapy or the duration of levodopa therapy was not closely related to the development of any adverse reaction, while Hoehn and Yahr's stage and dosage levodopa had the most significant influence on the development of adverse reactions. Therefore, levodopa therapy may not be an important risk factor of adverse reactions even when it is started early after the onset of Parkinson's disease. In order to prevent adverse reactions to long-term levodopa therapy in Parkinson's disease, it is important to minimize the dose of this drug even when it is administered in combination with multiple anti-Parkinsonism drugs.