SummaryNormal plasma contains an activity known as cofactor which further lengthens the clotting time of the plasma of some patients with the “lupus anticoagulant.55 Cofactor has been characterized as either prothrombin or a gamma globulin. Our findings indicate that cofactor has the following properties: stable at room temperature but largely destroyed by heating for 30 min at 56° C; sparingly adsorbed by Al(OH)3 or BaS04; apparent molecular weight on gel filtration around 200,000 daltons ; precipit- able between 50-75% ammonium sulfate saturation. Cofactor was present in plasmas from patients with hereditary deficiencies of factor II, V, VII, VIII, IX, X, XI, XII, or Fletcher factor; however, less cofactor activity was demonstrable in plasmas deficient in factor II, V, or X than in normal plasma or the other deficiency plasmas. Plasma from patients receiving oral anticoagulant therapy had variable levels of cofactor activity which could not be correlated with levels of factor II, VII, IX, X, or staphylocoagulase-reacting factor. Cofactor activity was unaffected by treatment with an anti-human immunoglobulin antiserum. These data support the conclusion that the cofactor reacting with our patient’s “lupus anticoagulant55 is neither prothrombin nor an immunoglobulin, but rather a unique molecule with some properties in common with each.