The metabolism of a substrate is closely linked to that of its cofactor(s). In the case of homocysteine, the vitamins B12, B6 and folic acid are involved in its metabolism, acting as coenzymes. To evaluate the role of these vitamins as determinants of homocysteine concentration in the healthy population, only data from this group should be considered. Studies dealing with vitamin deficiency and the occurrence of elevated homocysteine levels as well as with the treatment of elevated homocysteine levels by supplementing one or more of the vitamins have to be omitted. In the healthy population with "normal" homocysteine levels and a vitamin status currently regarded as adequate, folate seems to play the most important role in determining the blood homocysteine level. This has been derived from supplementation studies as well as from statistical correlation analysis regarding the relationship of the three vitamins to homocysteine. Until now, recommended dietary allowances for folate have been defined on the basis of the absence of clinical signs of deficiency as well as morphological alterations of blood cells indicating an early stage of folate deficiency. However, these recommended dietary allowance values do not seem to be sufficient when looking at homocysteine as a functional parameter of folate status. Due to the important role of folate status as a determinant of homocysteine concentration, it may be necessary to redefine an adequate blood folate level and probably reformulate dietary allowances for this B-vitamin.