Moderate elevations of plasma levels of homcyst(e)ine (hyperhomocyst-(e)inemia) are associated with cerebrovascular, peripheral vascular and coronary artery disease in retrospective case-control studies. The strength of this association appears stronger in peripheral and cerebrovascular disease. The molecular basis of hyperhomocyst(e)inemia is not fully understood. Environmental factors such as folate or vitamin B12 deficiencies, and genetic defects such as heterozygous crystathionine β-synthase deficiency or anomalies of 5',10'-methylene tetrahydrofolate reductase may contribute to elevated plasma homocyst(e)ine levels. The pathogenesis of homocyst(e)ine-mediated vascular damage may be multifactorial, including a possible toxic effect of intracellular accumulation of homocyst(e)ine, increased platelet activation and enhanced thrombosis mediated through the protein C system.