Patients with leg ulcers caused by venous insufficiency often show evidence of previous deep venous thrombosis. Resistance to activated protein C (APC resistance) is a newly identified, autosomal dominant inherited defect in the anticoagulant system which significantly predisposes affected individuals to develop venous thrombosis. To elucidate the significance of APC resistance in venous leg ulcer patients, APC resistance was determined in plasma samples obtained from 46 unselected, consecutive patients with venous leg ulcers, admitted to hospital during a 6-month period. Twelve of the 46 patients (26%: 95% confidence limits, 14-41%) had APC resistance. APC resistance is thus a common anticoagulant deficiency among patients with venous leg ulceration and should be considered a risk factor for the development of venous leg ulcer disease.