The present study describes a clinical trial in which Spanish patients suffering from peripheral vascular disease (Fontaine stage II) were given specific lipid supplements. Designed as a longitudinal intervention study, patients were provided with olive oil for 3 months, followed by a 3 month wash-out period, then supplemented with a combination of fish oil and olive oil for the final 3 months. Changes in plasma and lipoprotein fatty acid composition and susceptibility of LDL to in vitro oxidation were examined. Furthermore, lipid-supplement-induced changes in LDL properties were measured as relative electrophoretic mobility and macrophage uptake. In addition, thirteen patients not provided with olive oil and fish oil were included as a control group and twenty healthy age-matched individuals were used as a reference group. A complete clinical study and a nutritional survey concerning food habits and lifestyle were performed every 3 months. Yao indices and claudicometry did not change significantly with dietary intervention although changes in plasma lipid composition suggested an improvement in the condition of the patients. The intake of the fish-oil supplement resulted in significantly increased plasma levels of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) in comparison with baseline concentrations, olive-oil and control groups. Fish-oil consumption significantly decreased plasma triacylglycerol levels compared with the olive-oil period, control and reference groups. The susceptibility of LDL to Cu-mediated oxidation was lower in the patients consuming olive oil and the fish-oil supplement than in the control group, and the uptake of LDL by macrophages was significantly lower in the group supplemented with fish oil. In conclusion, consumption of olive oil together with a dietary supplement of fish oil may be useful in the nutritional management of patients suffering from peripheral vascular disease in terms of increasing plasma n-3 long-chain polyunsaturated fatty acids and decreasing susceptibility of LDL to oxidation.