Increased blood viscosity occurs in patients with claudication. This increase in viscosity, which is mainly due to elevated fibrinogen levels and a decreased red cell deformability, adversely influences blood flow. In addition to a positive effect on blood pressure, blood lipids, and platelet responsiveness, fish oil may improve blood flow due to a favorable influence on hemorrheology. In a prospective, randomized, double-blind study, we evaluated the effect of six capsules of fish oil (1.8 g eicosapentaenoic acid and 1.2 g docosahexaenoic acid) versus six capsules of corn oil (3 g linoleic acid), administered for 4 months, on walking distances, pressure indices during rest and after exercise, blood pressure, red cell deformability, fibrinogen, and lipid levels in 32 patients with stable claudication. No significant changes in walking distances and pressure indices during rest and after exercise occurred, despite a significant increase in red cell deformability in the fish oil group. Fibrinogen levels did not change in either group. In the fish oil group, a favorable change in blood lipids was noted; high-density cholesterol increased and triglycerides decreased. Mean arterial blood pressure declined to a similar extent in both groups. Thus, short-term supplementation with fish oil does not lead to clinically significant improvement of symptoms in patients with stable claudication. This suggests that red cell deformability is of minor importance in the arterial blood flow in the legs of these patients.