The aim of the study was to determine whether folic acid treatment in subjects with homocysteinemia would change their coagulation and oxidative status. Thirty-three patients with peripheral vascular disease and 26 elderly subjects with no symptoms of atherosclerosis, all of whom had total homocysteine >20 microM, were treated with folic acid (5 or 10 mg) for 3 months. In the 33 patients with peripheral vascular disease, homocysteine levels decreased from a median of 26.7 microM at baseline to 20.0 microM (p < 0.0001), whereas in the 26 asymptomatic elderly subjects, homocysteine level decreased from 24.4 microM to 18.6 microM (p < 0.0001). Plasma fibrinogen decreased whereas plasminogen and anti-thrombin increased; the differences between pre- and posttreatment values were significant in both patients and healthy subjects. Oxidative status markers showed a shift toward lower oxidative stress. This effect was observed in both study groups. An association of the therapeutic effect with the genetic polymorphism of 5,10-methylenetetrahydrofolate reductase was not detected. Folic acid supplementation to hyperhomocysteinemic subjects resulted in a decrease in total blood homocysteine concentrations; moreover, there was a tendency to reverse the coagulation status and oxidative stress.