In clinical practice, two potent and selective catechol-O-methyl transferase (COMT) inhibitors are available for the control of motor fluctuation in patients with Parkinson's disease. However, because of the complexity of fluctuating motor symptoms, it is difficult to evaluate the clinical efficacy of COMT inhibitors in each individual. Therefore, an objective factor predicting the clinical efficacy of COMT inhibitors is needed. Individual variation in COMT activity is regulated by a single nucleotide of theCOMTgene on the long arm of chromosome 22. Therefore, there could be a correlation betweenCOMTgenotype and the clinical efficacy of COMT inhibitors.Three double-blind studies evaluating the efficacy of a single or repeated doses of a COMT inhibitor failed to find significant difference in the improvement in the duration of daily ‘on’ time and degree of motor abilities between patients with differentCOMTgenotypes. Furthermore, there were no significant differences in the severity and frequency of dopaminergic adverse effects between patients with differentCOMTgenotypes. These data suggest that theCOMTgenotype is not a major factor in deciding the clinical efficacy of COMT inhibitors.