OBJECTIVE: The C677T polymorphism of the 5, 10 methylenetetrahydrofolate reductase (MTHFR) gene is associated with decreased MTHFR activity and elevated plasma homocysteine levels with the result of an increased risk for vascular disease. Because thrombosis of the maternal spiral arteries can be one of the causative events in the disease it has been suggested that the C677T polymorphism may also play a role in the pathogenesis of preeclampsia. Our case-control study investigated the prevalence of the 677T allele in two ethnically different populations and the potential association of the 677T allele with preeclampsia. Special attention was paid to the potential contribution of the fetal genotype to disease risk. METHODS: Blood samples were collected from 81 mothers and 61 newborns after preeclampsia and 99 mothers and 61 newborns with normal pregnancies. Genomic DNA was amplified by polymerase chain reaction with locus-specific primers and presence of the polymorphism was determined by enzymatic digestion with HinfI and visualization on polyacrylamide gels. RESULTS: Genotypes carrying the MTHFR 677T allele were significantly more frequent in German-Croatians than in Indonesians in both patients and controls (P = .0033 in controls). In contrast the prevalence of genotypes with the 677T allele was not increased among patients with preeclampsia compared with controls in both ethnic groups (P > .5 in all groups). In Germans the frequency of 677T homozygotes among controls even exceeded that observed in preeclamptic patients (677T/T genotype frequency 0.20 in controls and 0.07 in patients). We did not find an increased prevalence of paternally inherited 677T alleles in preeclamptic fetuses relative to controls or other signs of maternal-fetal transmission distortion. CONCLUSION: In our study the MTHFR C677T polymorphism was not associated with an increased risk for preeclampsia on the level of the maternal or fetal genotype. However significant differences of the frequency of genotypes carrying the 677T allele between Middle-Europeans and Indonesians were identified.