OBJJECTIVE: To determine the genotypes of four candidate genes in Japanese women with a history of preeclampsia, and in a control group of parous woman. STUDY DESIGN: Fifty-two pregnant women with a history of preeclampsia in their first pregnancy and 113 normotensive gravid women were studied. All subjects were Japanese women with singleton gestations. Genomic DNA was extracted, and genotypes of angiotensinogen (AGT), methyleneteterahydofolate reductase (MTHFR), factor V Leiden, and prothrombin genes were analyzed. RESULTS: The frequencies of homozygous AGT gene mutation and homozygous MTHFR gene mutation in preeclampsia were significantly higher than that in control. The calculated risk associated with the presence of both mutations did not exceed the risk with polymorphism of each gene. None of the examined cases showed polymorphism of factor V Leiden and prothrombin G20210A genes. CONCLUSION: In Japanese patients with preeclampsia, the angiotensinogen gene and particularly MTHFR gene may play a role in the pathogenesis of preeclampsia.