Activated protein C resistance caused by factor V Leiden is an important thrombophilia disorder which predisposes to venous thromboembolism. Some studies also suggest a role in the pathogenesis of arterial thrombosis and atherosclerosis. The authors have investigated the prevalence of activated protein C resistance and factor V Leiden in a series of 45 patients with peripheral vascular disease. Twelve patients were receiving warfarin. The activated protein C resistance ratios were significantly lower in the group of 33 non-warfarinized patients with peripheral vascular disease (median 2.82 (range 1.36-3.83)) compared with 33 age- and sex-matched controls (median 2.97 range 2.24-4.11); P<0.005; Wilcoxon rank sum). Eight patients (24%) had activated protein C resistance (ratio <2.2). The prevalence of factor V Leiden in patients with peripheral vascular disease was 17.8% (8/45). This is significantly increased compared with the local population and UK published frequency of 3.5% for this genotype. The presence of factor V Leiden did not affect the late outcome of arterial reconstructive surgery in terms of graft patency (P=0.5, Fisher's Exact test).