The methylenetetrahydrofolate reductase (MTHFR) gene variant C677T is suspected to be a risk factor for psychiatric disorders, but it remains uncertain whether the MTHFR C677T variant is associated with bipolar disorders. To investigate possible association, unrelated controls (n=461) with no history of psychiatric disorders and patients (n=501) diagnosed with bipolar disorder were recruited in this study. In addition, six association studies published up to June 2008 were included in a subsequent meta-analysis. No significant difference was found in either allele frequencies or genotype distribution between patients and controls in our association study in the Chinese population. Similarly, the meta-analysis result showed no significant association between MTHFR C677T and bipolar disorder. In conclusion, the MTHFR C677T variant is unlikely to play a major role in the susceptibility to bipolar disorder, although MTHFR plays an important role in the one-carbon metabolism and DNA methylation.