Motor fluctuations are the most common complication of levodopa therapy for Parkinson's disease (PD). Genetic factors could play a role in determining the occurrence of motor fluctuations. To investigate whether dopamine receptor D5 (DRD5) T978C polymorphism is associated with the risk of developing motor fluctuations in PD, we studied this polymorphism in a case-control study of 120 subjects with sporadic PD and 110 control subjects. We found that the overall allelic and genotypic frequencies did not differ significantly between patients with PD and control subjects (all P>0.7), and between motor fluctuators (n=50) and non-motor fluctuators (n=50) (all P>0.8). It suggests that DRD5 T978C polymorphism is not associated with the susceptibility to PD, nor with the risk of developing motor fluctuations in PD. Therefore, other polymorphisms that alter the expression of the dopamine receptors should be further studied.