Fasting total plasma homocysteine levels were measured by rapid ion-exchange chromatography in 100 patients with symptomatic atherosclerotic peripheral vascular disease (PVD) and 100 age and sex-matched control subjects. Demographic data, biochemistry, hematology, and lipid fractions were measured in both groups, and clinical and vascular laboratory disease parameters were recorded for the patient group. Patients with hyperhomocysteinemia (defined as those with fasting homocysteine values exceeding the 90th percentile of the control range) were compared to patients with normal homocysteine with respect to the above parameters. Total fasting homocysteine concentrations were significantly higher in the patient group (28.8 +/- 14.9 mumol/l) than in the control subjects (20.3 +/- 11.3 mumol/l; p < 0.001). Homocysteine levels were also higher in males than in females in both the control and the patient groups. Homocysteine correlates positively only with age in the healthy controls (r = 0.291; p < 0.005) but not with other standard risk factors. Multivariate analysis of the biochemical risk factors confirmed that total plasma homocysteine concentration is an independent risk factor for PVD (p < 0.001). Hyperhomocysteinemia is not associated with vitamin B12 or folate deficiency states. Vitamin B12 concentration was 591 +/- 313 ng/l in the control group, and 682 +/- 405 ng/l in the patient group (p = NS). Serum folate concentration was lower in the controls (7.2 +/- 2.3 micrograms/l) than in the patients (8.3 +/- 2.0 micrograms/l, p < 0.001). Mild hyperhomocysteinemia was detected in 27% of the patients. Patients with hyperhomocysteinemia has a four-fold increase in risk of PVD relative to patients with a normal homocysteine level. There is no significant difference between the two groups with respect to patient demographics, biochemical risk factors, and disease pattern and severity.