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; 2 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. (C) 2003 Elsevier B.V. All rights reserved.