Epigenetic mechanisms such as methylation of DNA, could lead to abnormal neurodevelopment and may be important in the etiology of schizophrenia. Maternal dietary folate intake may play a role in determining methylation levels. The MTHFR gene C677T polymorphism influences folate metabolism and intracellular availability of folate metabolites for methylation. We carried out a meta-analysis of MTHFR C677T genotype and schizophrenia risk, and found that TT homozygotes had a significantly increased risk, OR 1.48 (1.18–1.86). This supports the hypothesis that folate status is a determinant of schizophrenia risk. Larger studies of this issue are required, together with studies of maternal genotype which could identify whether maternal folate status during pregnancy is important. © 2005 Wiley-Liss, Inc.