The effectiveness of continuous infusion porcine factor VIII (PFVIII) has been evaluated in the treatment of 7 consecutive patients with factor VIII(FVIII) inhibitors. Two patients had hemophilia A and five were nonhemophiliacs with acquired FVIII inhibitors. The median pretreatment anti-porcine FVIII titre was 0.2 (range: 0-15.0) Bethesda units (BU), and the anti-human FVIII titer was 12.0 BU (range: 2.4-50.0). All patients presented with major bleeding. Patients were given a bolus dose of PFVIII followed by continuous infusion. Six patients also received immunosuppressive therapy. Therapeutic FVIII levels (>0.5 U/ml) were achieved in 6 of 7 patients at a median time of 12.5 hr, and then maintained with continuous infusion PFVIII. Six patients were treated for more than 7 days, and in four of these there was a decline in FVIII recovery between days 7 to 11, presumably related to a rising antibody response to PFVIII. These four patients were plasmapheresed and the three patients with autoantibodies recovered therapeutic FVIII levels but this did not occur in the patient with hemophilia. Thrombocytopenia developed in 4 patients at days 18 to 24, with the platelet count falling to 11 to 87 ร 10 9 /L, and the PFVIII was discontinued in 3 patients. All patients recovered from the acute bleeding events. With prolonged immunosuppressive therapy, the FVIII inhibitor disappeared in all patients with autoantibodies and there have been no relapses after a median follow-up period of 581 days. This study demonstrates that continuous infusion PFVIII is an effective therapy for patients with FVIII inhibitors, but that prolonged treatment is associated with the development of inhibitors to porcine FVIII and severe thrombocytopenia, which readily corrects with discontinuation of PFVIII. Am.