This study examined the association of plasma homocysteine levels and the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with schizophrenia in the Han population residing in northern China. We detected the MTHFR C677T genotype in 123 schizophrenia patients and compared it with the genotype of 123 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, by using the cyclophorase method, the plasma homocysteine concentration in 62 schizophrenia patients was determined and then compared with that in 62 controls; these 62 patients and 62 controls were a subset of the 123 patients and 123 controls. We found that the homocysteine levels in the patients were significantly higher than those in the controls. The frequency of homozygosity for the 677T allele of the MTHFR gene was higher in the patient group than in the control group, and the difference between the two groups was statistically significant for both the MTHFR genotype and the frequency of allele homozygosity. A significant difference was observed in the plasma homocysteine levels among the different genotypes in the patient and control groups. In conclusion, both elevated plasma homocysteine levels and variation in the MTHFR 677C-->T gene are related to increased rates of schizophrenia and are risk factors for schizophrenia.