Down syndrome (DS) is generally considered as an "atheroma-free model". In this preliminary study, we investigated homocysteine, folate and Vitamin B(12) levels in 13 DS patients (male, average age 60 years) and 20 age-matched individuals. We also studied lipid fractions, and polymorphisms for Cystothionine beta-synthase (CBS), 5,10-methyl-tetrahydro-folate reductase (MTHFR) and apolipoprotein E (Apo-E) genes. However, DS patients with the MTHFR TT genotype showed an increased of plasma homocysteine (tHcy). Our results indicate that this group of "healthy old" Down syndrome patients, although showing some classical biochemical risk factors for atherosclerosis, did not suffer clinical cardiovascular alterations.