A 78-year-old man and an 81-year-old woman without hemophilia suddenly developed giant ecchymoses and intramuscular hemorrhage. Prolonged activated partial thromboplastin time and low factor VIII activity were observed, and the patients were subsequently diagnosed as having acquired factor VIII inhibitors. The patients were infused with one dose of recombinant factor VIII, 50 to 100 U/kg body weight, followed by cyclophosphamide, 500 mg on day 1 and 200 mg/day on days 2 to 5; vincristine, 2 mg on day 1; and prednisolone, 100 mg/day on days 1 to 5 (recombinant factor VIII-CVP therapy). Both patients responded after one course of therapy. Disappearance of inhibitors was achieved after three to four courses of therapy without subsequent recurrence. Recombinant factor VIII-CVP therapy is safe and effective in the eradication of factor VIII inhibitors.