Motor fluctuations complicate therapy in Parkinson's disease (PD). The mechanisms responsible for motor fluctuations such as the on-off type, are poorly understood. Differences of activity of various enzymes, such as Catechol-O-Methyltransferase (COMT, E.C.2.1.1.6.) may influence the appearance of motor fluctuations and the quantity of metabolic products of levodopa. Aim of this study was to compare erythrocyte COMT-activity in Parkinsonian patients without and with motor fluctuations from the on-off type. No significant differences in COMT-activity appeared in both groups. We conclude that activity differences in COMT-activity do not contribute to the appearance of motor fluctuations in Parkinson's disease.