The development of antibodies to factor VIII (circulating anticoagulant, factor VIII inhibitor) is a serious complication following substitution therapy in patients with hemophilia A. These antibodies are rarely specific of human factor VIII, tending to cross-react to a variable extent with factor VIII from other species. Their neutralizing activity is usually weaker against porcine than human factor VIII. In this study, anti-human and anti-porcine factor VIII antibodies (Ab) were measured in 41 patients with severe hemophilia A. The anti-human Ab titers ranged from 0.5 to 1200 BU/ml, and the anti-porcine Ab titers ranged from 0 to 170 BU/ml. The median cross-reactivity was 28% (mean 28.9 +/- 17.2%, range 0-75%). Of the 24 patients with anti-human Ab titers > 5 BU/ml, 11 (46%) had a low anti-porcine Ab level (< or = 5 BU/ml). These patients could be treated effectively with porcine factor VIII concentrate (Hyate: C).