Human serum paraoxonase 1 is a calcium-dependent esterase located on high density lipoproteins (HDL). It inhibits LDL peroxidation and hydrolysis of oxide forms of phospholipides and therefore significantly affects the development of ateroscletosis. The aim of this study was to establish the paraoxonase and arylesterase activity of PON1 in adult people with Down syndrome (DS). Adults with DS (10 men and 10 women ages 16 to 37 years) participated and were compared to a control group (10 men and 10 women age ranging from 17 to 45 years). The 55(L/M) and 192(Q/R) DNA polymorphism (PCR-RFLP method) and paraoxonase and arylesterase activity was investigated in every patient. The results showed the reduction of PON1 activity in people with DS, in contrast to the decreased development of atherosclerosis in DS. Therefore it can be concluded, that PON1 does not have a direct effect on the lower prevalence of atherosclerosis in people with DS.