BACKGROUND. Homocysteine (HCY) was recently established as an independent risk factor for atherosclerosis, The prevalence of an increased homocysteine plasma concentration was reported to be up to 6-fold higher in patients with different locations of arterial occlusive diseases. AIM. This study evaluated critically whether the total HCY plasma concentration can be used as a screening marker for peripheral arterial disease in the general population. METHODS. Study subjects were 40 patients (51.8 +/- 7.5 years) with symptomatic lower limb peripheral arterial disease (PAD) (stage II) and 40 healthy volunteers (45.6 +/- 6.8 years, P < 0.05 vs PAD). The percentage of women in both groups was 30%. The plasma HCY concentration was determined by using derivatization techniques and subsequent fluorescence high-performance liquid chromatography. RESULTS. Total plasma HCY concentration was significantly higher in the PAD group than in controls (14.90 +/- 5.78 CIM vs 11.32 +/- 2.95 <mu>M, respectively, P < 0.001). Also, the coefficient of variation of plasma HCY in PAD was significantly higher than that in the control group. 0.38 vs 0.25 (P < 0.001), respectively, reflecting greater interindividual differences. In addition to a PAD-specific effect, the plasma HCY concentration was also dependent on gender and age (both P < 0.05). Sensitivity and specificity of HCY as a marker of PAD were 0.3 and 0.95, respectively. Positive and negative predictive values were 0.85 and 0.42, respectively. CONCLUSIONS, From these data it is concluded that HCY metabolism may have an influence on the development of PAD in one-third of all patients with PAD, and that total plasma HCY concentration may not be suited as a screening test for PAD in the general population but rather serves as a monitoring marker in certain risk groups.