Highly purified porcine factor VIII:C (FVIII:C) concentrate prepared by polyelectrolyte fractionation has been available for therapeutic use since 1980. Over the last decade substantial international experience has confirmed the value of porcine FVIII:C in management of hemophilia with inhibitors, and recent studies have underlined its particular effectiveness in treating patients with the acquired form of the disease. The rationale for use of porcine FVIII:C is based on a twofold premise. First, most inhibitors interact less strongly with porcine FVIII:C than they do with the human factor; cross-reactivity is especially low, and often negligible, among patients with acquired disease. Second, when measurable levels of circulating FVIII:C can be achieved, the likelihood of clinical hemostasis is maximized. In a variable proportion of patients with the congenital disease, anamnestic rises in titers of the inhibitor against human FVIII:C may follow treatment with the porcine factor, and this phenomenon may constrain therapy. These events seem to occur rarely in persons with acquired inhibitors, however, thus broadening therapeutic application of porcine FVIII:C to these patients. Although anamnesis often is perceived as a limitation, significant untoward transfusion reactions are highly unusual after porcine FVIII:C therapy. Although early experience with this form of treatment centered on management of major bleeding episodes and hemostatic crises, use of porcine FVIII:C has more recently been extended to more routine bleeding problems, immune tolerance induction regimens, prophylaxis, and home therapy. These and other advances are discussed.