Elevated plasma homocysteine (tHcy) is a risk factor for Alzheimer's disease (AD), and thus B vitamins may have a role in the prevention of AD. The objective of this study was to determine if tHcy lowering vitamins decrease the circulating levels of A-beta protein 1-40 (A beta 40). We randomized 299 older men to treatment with 2mg of folate, plus 25mg of B6 and 400 microg of B12, or placebo. After 2 years of treatment the mean (S.E.) increase of A beta 40 was 7.0 pg/ml (8.4) in the vitamin group (4.9%), and 26.8 pg/ml (7.7) (18.5%) in the placebo group. We conclude that B vitamins may decrease the plasma level of A beta 40 and have a role in the prevention of AD.