Objective: Authors determined the impact of high-dose vitamin supplements on plasma homocysteine levels in patients with Alzheimer disease (AD). Methods: Authors used an open-label trial of folic acid, vitamin B12, and vitamin B6, in combination for 8 weeks, with measurement of plasma homocysteine levels in the fasting state and after methionine-loading. A total of 69 subjects with AD were enrolled, including 33 who were taking standard multivitamin supplements; 66 were available at 8-week follow-up. Results: The high-dose vitamin regimen was associated with a significant reduction in fasting and postmethionine-loading homocysteine. Reductions were greater in the subgroup not using multivitamins, but were also significant in the multivitamin users. Conclusion: High-dose vitamin supplementation reduces homocysteine levels in patients with AD. The effect of supplementation on rate of cognitive decline will be assessed later in a randomized, double-blind study.