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In this valedictory address the research of the Nijmegen homocysteine team on birth defects and vascular disease is presented. Hyperhomocyst einemia was found in women with neural tube defect (NTD) offspring, ot her birth defects and vascular disease. Raised homocysteine levels in the blood plasma can be explained by lack of B-vitamins (folic acid), mutation of the 5,10-methylenetetrahydrofolate reductase genes or both . Genetic mutations were found on the first chromosome (677 C-->T and 1298 A-C) and can explain up to 50% of the NTD protective effect of fo lic acid. The inborn error of methionine-homocysteine metabolism was a lso found in cases with recur-rent early pregnancy loss, schisis, cong enital heart defects and vascular problems like placental abruption. i nfarcts and fetal growth retardation. One of the most exciting medical findings of the last years is that folic acid can prevent NTD defects . This might also hold for other birth defects and vascular disease. ( C) 1998 Elsevier Science Ireland Ltd.