The eradication of a high-response Factor VIII inhibitor in patients with severe hemophilia A is extremely rare even with prolonged immunosuppressive therapy. This report presents a patient with severe hemophilia A, in whom the disappearance of such an inhibitor coincided with the development of the acquired immunodeficiency syndrome (AIDS). Laboratory studies demonstrated a marked decrease in helper T-cells and marked depression of cell-mediated immunity by in vivo and in vitro testing. In addition, humoral immune responses were abnormal. Thus, anamnestic antibody formation to different antigens was absent and in vitro pokeweed mitogen-induced immunoglobulin synthesis by the patient's B-cells was markedly impaired even in the presence of normal T-cells. These findings indicate that the disappearance of the Factor VIII inhibitor and the lack of an anamnestic antibody response to infused Factor VIII observed in this patient may be secondary to a humoral immunodeficiency associated with AIDS.