The aim of this study was to determine the levels of plasma fatty acids in patients with peripheral arterial disease and in control subjects and to identify whether any risks of disease related to these differences were influenced by smoking and antioxidant intake. A random sample of 1592 men and women aged 55 to 74 years was selected from the general population (the Edinburgh Artery Study), from which 153 cases of peripheral arterial disease were identified by the presence of intermittent claudication and low ankle systolic pressures at rest and during reactive hyperemia; these were matched by age and sex to 153 control subjects with no evidence of cardiovascular disease. In 113 case and 122 control subjects, fatty acid levels were measured in three plasma fractions (triglyceride, cholesteryl ester, and phospholipid), and smoking habits and dietary antioxidant intake were determined by questionnaire. Arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid (DPA/ T he main dietary essential fatty acids are linoleic acid (18:2 n-6) and a-linolenic acid (18:3 n-3), both found mainly in vegetable oils. Within the body, these parent essential fatty acids are metabolized by a series of reactions to form arachidonic acid and eicosapentaenoic acid (EPA), which are further metabolized to prostacyclins and thromboxanes (Figure), substances known to exert opposing physiological effects on the cardiovascular system. An important rate-limiting step in the metabolism of linoleic acid and a-linolenic acid is the initial desaturation reaction, where the two parent fatty acids compete for the A-6-desaturase enzyme. This step may also be inhibited by several factors associated with cardiovascular disease, such as high cholesterol levels, catecholamines, high saturated-fat intake, and aging.1 It is therefore possible for some individuals to be effectively lacking in essential fatty acid metabolites, despite an adequate dietary intake of linoleic and a-linolenic acids.