To investigate the role of methylenetetrahydrofolate reductase gene polymorphisms in schizophrenia, we analyzed the genotypes of MTHFR677 and MTHFR1298 of 130 schizophrenic patients and 226 controls, using a polymerase chain reaction restriction fragment length polymorphism method. The MTHFR T677 allele was significantly distributed (chi(2)=7.900; P=0.019), between schizophrenic cases and healthy controls. The T677T genotype was overrepresented in the schizophrenic patients (OR=2.504; 95% CI=1.276-4.915; chi(2)=7.477; P=0.006). The T677T/A1298A, and C677T/C1298C compound genotypes were greater in the schizophrenic patients (OR=3.157; 95% CI=1.522-6.545; chi(2)=10.336; P=0.001 and OR=1.744; 95% CI=0.108-28.121; chi(2)=0.158; P=0.691, respectively). The MTHFR T677 allele and T677T and T677T/A1298A genotypes are genetic risk factors for schizophrenia.