Activated Protein C (APC) is an important regulatory protein which helps to maintain the balance of procoagulant and anticoagulant properties within the circulation. It acts by cleaving activated factor V and activated factor VIII, limiting clot formation at the appropriate level. An abnormal factor V which is resistant to cleavage by APC has been described recently in patients with venous thrombosis. We have set up an assay utilizing DNA amplification of the portion of the factor V gene responsible for its resistance to APC. An abnormal cleavage pattern of the DNA product is seen using a restriction enzyme in patients with this mutation which can be correlated with a functional (clotting) assay in screening patients at risk.